|SYMPOSIUM - CERVICAL SPONDYLOMYELOPATHY
|Year : 2019 | Volume
| Issue : 1 | Page : 52-58
Ossification of the posterior longitudinal ligament: Etiology, prevalence, progression, and surgical strategies
Department of Orthopaedic Surgery, Faculty of Medicine, University of Toyama, Toyama, Japan
|Date of Web Publication||11-Jan-2019|
Dr. Yoshiharu Kawaguchi
Department of Orthopaedic Surgery, Faculty of Medicine, University of Toyama, 2630, Sugitani, Toyama 930-0194
Source of Support: None, Conflict of Interest: None
Ossification of the posterior longitudinal ligament (OPLL) is characterized by replacement of the ligamentous tissue by ectopic new bone formation. OPLL often causes narrowing of the spinal canal and has been recognized as a cause of cervical myelopathy and/or radiculopathy. Although a clear inheritance of OPLL has not been identified, there is a strong genetic background for OPLL. A recent genome-wide association study using all Japan cohort reported that there were 6 susceptible loci for OPLL. In addition, there were several studies to seek the biomarkers of OPLL. OPLL is frequently found in the cervical spine. However, 53.4% had OPLL not only in the cervical spine, but also in other spinal regions in patients with cervical OPLL. Further, 65.2% with cervical OPLL had ossification of the ligamentum flavum (OLF) especially at the levels of the thoracic and the lumbar spine. There is no effective conservative treatment. Surgical decompression is considered in patients with severe and/or progressive myelopathy. Early surgical decompression of the spinal cord is recommended in patients with apparent myelopathy. Operative methods are divided into two procedures, anterior decompressive surgery and posterior decompressive surgery. The choice of the surgical procedure is determined according to several factors, such as local pathology of OPLL and spinal alignment.
Keywords: Ossification of the posterior longitudinal ligament (OPLL), surgery, radiological characteristics, natural history of OPLL, management
|How to cite this article:|
Kawaguchi Y. Ossification of the posterior longitudinal ligament: Etiology, prevalence, progression, and surgical strategies. Indian Spine J 2019;2:52-8
|How to cite this URL:|
Kawaguchi Y. Ossification of the posterior longitudinal ligament: Etiology, prevalence, progression, and surgical strategies. Indian Spine J [serial online] 2019 [cited 2019 May 23];2:52-8. Available from: http://www.isjonline.com/text.asp?2019/2/1/52/249898
| Introduction|| |
Ossification of the posterior longitudinal ligament (OPLL) is characterized by the replacement of the ligamentous tissue through ectopic new bone formation [Figure 1] and [Figure 2]. OPLL commonly leads to the narrowing of the spinal canal and is recognized as a cause of cervical myelopathy and/or radiculopathy [Figure 3]., Several OPLL cases have been reported in Asian countries, especially in Japan. However, OPLL is now also known to be observed in Caucasians. The incidence of OPLL is estimated at about 3% in Japan, 0.2%–1.8% in China, and 0.95% in Korea, while it was 0.12% in the United States and 0.1% in Germany. Although OPLL was first reported in 1960, the pathogenesis remains unknown. With respect to treatment, medication is ineffective in halting the development of OPLL, and surgical treatment is sometimes very challenging in clinical practice. Numerous issues regarding this disease need to be resolved in the future. In this review, we focused on the etiology, radiological characteristics, and surgical strategy for OPLL with the most recent scientific findings. A systematic computerized literature search was performed using Cochrane Database of Systematic Reviews, Embase, and PubMed. The publications made over the past 10 years were analyzed. The searches were performed using Medical Subject Headings and the subheadings used were “OPLL,” “epidemiology,” “etiology,” “management,” “surgery,” and “therapy.”
|Figure 1: Plain radiographs of the cervical spine. (a) Normal volunteer, (b) a patient with ossification of the posterior longitudinal ligament. Arrows show ossification of the posterior longitudinal ligament|
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|Figure 2: Computed tomography of the cervical spine. (a) Normal volunteer, (b) a patient with ossification of the posterior longitudinal ligament. Ossification of the posterior longitudinal ligament narrows the spinal canal|
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|Figure 3: Magnetic resonance imaging of the cervical spine. (a and c) Normal volunteer, (b and d) a patient with ossification of the posterior longitudinal ligament. Ossification of the posterior longitudinal ligament reveals compression of the spinal cord (axial T2WI) (d)|
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| Etiology|| |
Although a clear inheritance of OPLL has not been identified, there is a strong genetic background for OPLL. A nationwide survey of pedigree in Japan showed radiographic evidence of OPLL in 23% of all blood relatives and 29% of the brothers of the OPLL patients. In a twin pair study, OPLL was observed in 85% of both monozygotic twins. Recent genetic studies have identified six candidate genes for OPLL. A genome-wide association study (GWAS) conducted on all Japan cohort reported that 20p12.3 (rs2423294: P = 1.10 × 10 [−13]), 8q23.1 (rs374810: P = 1.88 × 10 [−13]), 12p11.22 (rs1979679: P = 4.34 × 10 [−12]), 12p12.2 (rs11045000: P = 2.95 × 10 [−11]), 8q23.3 (rs13279799: P = 1.28 × 10 [−10]), and 6p21.1 (rs927485: P = 9.40 × 10 [−9]) were the susceptible loci for OPLL. Among these genes, the further functional study revealed that encoding R-spondin 2 (RSPO2) is a susceptibility gene for OPLL. RSPO2 is known to be a secreted agonist of canonical Wnt-β-catenin signaling. RSPO2 is decreased in the early stages of chondrocyte differentiation. RSPO2 inhibits the expression of genes encoding early chondrocyte differentiation markers by activating the Wnt-β-catenin signaling. The most commonly associated single nucleotide polymorphism that was shown in the previous GWAS is located in the chondrocyte promoter region of RSPO2. A transcription factor, CCAAT-enhancer-binding protein β (C/EBPβ), specifically binds to the RSPO2 core promoter region containing rs374810. Thereafter, it increases the RSPO2 expression. The risk allele of rs374810 affects the binding of the promoter with C/EBPβ and decreases in vivo and in vitro RSPO2 transcription.
Studies using biomarkers also aim to identify OPLL pathogenesis. Our recent study revealed that the mean value of hypersensitive-C reactive protein (CRP) in the OPLL group was higher than that in the controls; we also found that the serum phosphate level in the OPLL group was lower than that in the control group. Further, a negative correlation was found between the serum phosphate level and OPLL severity, and the mean hypersensitive-CRP in the OPLL progression group was higher than that in the nonprogression group. We found a positive correlation between the average annual length of OPLL progression and the hypersensitive-CRP. Thus, inflammation and phosphate metabolism might be key factors in OPLL etiology. Several studies have investigated the biomarkers of OPLL. Markers for the Wnt/catenin signals and bone metabolic markers have been reported. A study that uses biomarkers may be very helpful in understanding the disease etiology. In contrast, OPLL often develops during middle age, that is, after 50 years of age. Thus, some environmental factors appear to be associated with the disease. OPLL is a multifactorial disease. These studies shall help clarify the mechanism of OPLL in the future.
| Radiological Characteristics|| |
OPLL is commonly found in the cervical spine. However, coexisting ossified lesions are sometimes observed in other spinal regions [Figure 4]. Our previous study revealed that 53.4% of the patients with cervical OPLL had OPLL not only in the cervical spine, but also in other spinal regions. Majority of the patients with multilevel OPLL are women, although the incidence of OPLL is higher in men. Further, 65.2% of the patients with cervical OPLL had ossification of the ligamentum flavum (OLF), especially at the levels of the thoracic and the lumbar spine, and 9.6% had OPLL and OLF at the same spinal level. This OLF lesion often compresses the spinal cord. Thus, computed tomography analysis of the whole spine is recommended in patients with radiographic evidence of OPLL in the cervical spine to enable early detection of additional ossification sites. Resnick et al. reported diffuse idiopathic skeletal hyperostosis (DISH) in 1975. OPLL might be a subtype of DISH.
|Figure 4: The whole spine computed tomography of 62-year-old female patient with ossification of the posterior longitudinal ligament. Ossification of the posterior longitudinal ligament is found not only in the cervical spine but also in the thoracic spine and the lumbar spine. Ossification of the ligamentum flavum is observed at T5-6 level where ossification of the posterior longitudinal ligament is also found|
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| Surgical Strategy For Ossification of the Posterior Longitudinal Ligament|| |
The clinical manifestation of cervical myelopathy caused by OPLL is highly varied. Patients with cervical OPLL frequently complain of neck pain, numbness in the upper and/or lower extremities, gait disturbance due to spasticity (spastic gait), hand clumsiness, and vesicoureteral (V-U) disturbance. The symptoms of thoracic myelopathy caused by thoracic OPLL are back pain, numbness below the trunk, spastic gait, and V-U disturbance. Of these symptoms, surgical decompression is considered in patients with long tract signs, such as spastic gait, hand clumsiness, and V-U disturbance. Patients who only have neck pain, back pain, and numbness in the upper and/or lower extremities should not be operated on because surgical decompression is not always effective for these symptoms.
Early surgical decompression of the spinal cord is recommended in patients with apparent myelopathy because long-lasting compression of the spinal cord may cause irreversible change in the spinal cord. We also recommend early surgical intervention in patients with moderate myelopathy because favorable surgical results are possible in such patients. Even if patients have mild myelopathy with severe spinal stenosis, surgery may be indicated. However, prophylactic operation is not recommended in asymptomatic OPLL patients because of the risk of surgery.
The operative methods are divided into the following two procedures: Anterior decompressive surgery and posterior decompressive surgery. Combined surgery, involving both anterior and posterior surgeries, is performed occasionally. Staged surgery is also considered for some patients. Most surgeons choose the surgical method as per the patient's general condition, OPLL type, and the severity of cervical myelopathy.
| Posterior Surgery|| |
Posterior surgery is a suitable method for cervical OPLL because cervical OPLL usually involves multilevel spinal cord compression. In posterior surgery, such as cervical laminectomy and laminoplasty, decompression is achieved by shifting the spinal cord posteriorly., Expansive cervical laminoplasty has become the standard technique for patients with myelopathy caused by OPLL [Figure 5]., There are two types of expansive laminoplasty – bilateral hinge type and the unilateral hinge type., In both the procedures of cervical laminoplasty, the laminae are preserved, and the spinal canal is expanded posteriorly. This technique of cervical laminoplasty is applied in patients with myelopathy due to OPLL and in patients with cervical spondylotic myelopathy (CSM). Long-term results of expansive cervical laminoplasty for OPLL treatment have been reported.,,, We have reported the results of follow-up of more than 20 years' postoperatively. Overall, the neurological recovery, as evaluated by the Japanese Orthopaedic Association score, was rapid within a year and continued to improve until 10 years after various surgical interventions for cervical laminoplasty. The maximum recovery rate after cervical laminoplasty for OPLL patients is reportedly about 50%–60%. However, it has been reported that 15%–30% of the patients show late neurological deterioration after the surgery.,,,, The types of late neurological deterioration include cervical lesions and noncervical lesions. Regarding the cervical lesions, the progression of cervical OPLL is one of the most common causes of deterioration. Three-quarters of the patients had OPLL progression during 10 years after en bloc laminoplasty. The patients who were younger than 50 years of age with the continuous type or mixed type have a high risk of progression., Other causes of cervical lesions are trauma and spinal cord atrophy. In contrast, ossified lesions in the thoracic spine, such as thoracic OLF and OPLL, become common causes of neurological deterioration in noncervical lesions.
|Figure 5: A 47-year-old female patient. (a) Preoperative plain radiograph, (b) plain radiograph after en bloc cervical laminoplasty. The spinal canal is enlarged|
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Several factors influence the final surgical outcomes. Older patient age (>60 years old),,,, long preoperative duration of symptoms (>1-year duration), traumatic onset,, occupancy ratio of OPLL in the spinal canal (>60%), and severe myelopathy, are poor preoperative prognostic factors. Kyphosis of cervical alignment and small area of the spinal cord have been indicated as preoperative local factors resulting in poor prognosis in OPLL patients, because it may make it difficult to achieve the shift of the spinal cord after laminoplasty in patients with cervical kyphosis.,, It is debatable whether the change in signal intensity shown in magnetic resonance imaging (MRI) is related to postoperative recovery. Several reports have described that high intensity in the spinal cord on T2-weighted MRI image indicated spinal cord damage and poor prognosis;,,,, however, there are some objections.,,,
With respect to the complications in cervical laminoplasty as well as posterior fusion surgery with instrumentation, many authors have pointed out the occurrence of segmental motor paralysis that mainly involves the C5 segment.,,,, The incidence of segmental paralysis following different types of laminoplasties reportedly ranges from 4% to 13% of all surgical cases., The precise causes remain unknown; however, surgical trauma, the tethering effect of the nerve root, an impingement of the stretched nerve root, and reperfusion injury of the spinal cord are believed to be the causal factors for this paralysis., The prognosis of this complication is usually good, with spontaneous regression within 1–2 years; however, this unfavorable condition continues in the long-term follow-up in some cases. Although the neurological outcome is improved after expansive cervical laminoplasty, some patients complain of axial symptoms, including pain and/or stiffness in the posterior neck and shoulder and a limited neck range of motion (ROM) following laminoplasty.,,, These complaints are observed not only in patients with OPLL but also in those with CSM following cervical laminoplasty. Several papers have described the possible mechanisms of the axial symptoms. Some researchers believe that the axial pains are caused due to damaged neck muscle and facet joints., The limited neck ROM might be attributable to the interlaminar fusion after laminoplasty. The neck ROM was reduced to 30%–60% of the preoperative value after the laminoplasty. In order to prevent these unfavorable effects, several intra- and post-operative measures are developed., Minimal invasive procedures, such as skip laminectomy and C7 preserved laminoplasty, are used. Further, the early exercise of the posterior neck muscle is recommended after cervical laminoplasty.
Some authors recommend posterior decompression and fusion surgery with instrumentation in patients with cervical OPLL because this surgical procedure prevents postsurgical kyphosis and postsurgical progression of OPLL. This procedure might be beneficial because correction of kyphosis and indirect decompression from OPLL might be achieved. However, the suitable area for fusion is yet to be clarified. The neck ROM is lost after fusion surgery; thus, fusion surgery in the cervical spine is carefully indicated.
| Anterior Surgery|| |
The anterior approach is ideal for surgical treatment in OPLL patients because OPLL exists anteriorly in the spinal canal. Some authors emphasize that anterior decompression is indicated in patients with massive OPLL, >6–7 mm in thickness or with an occupancy ratio of OPLL in the spinal canal >60%. The anterior approach is also recommended in patients with local kyphosis of the cervical spine. However, the anterior approach might require a long operation time and might be associated with massive intraoperative bleeding compared to posterior surgery. In addition, cerebrospinal fluid (CSF) leak is sometimes encountered during the removal of OPLL because the dura matter is frequently ossified in OPLL patients. The anterior floating method of OPLL for the decompression of the spinal cord was developed to minimize the surgical intervention as well as the risk of massive bleeding and CSF leak., Favorable long-term outcomes of anterior surgery have been reported. Late neurological deterioration is found in 20% of the patients. The causes of deterioration are inappropriate decompression, OPLL progression, other ossified lesions in the spinal canal, and diseases of the adjacent segment.
| Anterior Surgery Versus Posterior Surgery|| |
There is no consensus regarding the choice between anterior and posterior surgery. Each procedure has its own advantages and disadvantages., Anterior surgery is performed in patients with <2 level lesions of OPLL, while posterior surgery is performed for patients with >3 level lesions. A multicenter retrospective case–control study showed no significant differences in the postoperative neurologic recovery rate of the two procedures. The K line is a good indicator for choosing between anterior and posterior decompression. The K line is defined as a line that connects the midpoints of the spinal canal at C2 and C7. If OPLL does not exceed the K line; K line (+) group and if it does exceed the K line; K line (−) group. Posterior decompression is ineffective in patients with K line (−) group. Anterior decompression is beneficial in patients with K line (−) group. In contrast, our recent report demonstrated that 6 out of 139 patients (4.3%) with >3 years' follow-up required anterior decompression surgery after posterior decompression surgery, and neurological improvement was observed in all patients after anterior decompression surgery as a second surgery. Thus, staged surgery is also effective, and it might be considered that posterior decompression surgery with laminoplasty remains the initial treatment. Moreover, in patients with neurological deterioration during the follow-up, anterior decompression surgery is the salvage procedure.
| Surgical Treatment of Thoracic Ossification of the Posterior Longitudinal Ligament|| |
OPLL and OLF are also observed in the thoracic spine. Thoracic myelopathy that is caused by OPLL and/or OLF is generally progressive in nature and gives a poor response to conservative therapies. Therefore, surgical treatment is the only effective option. However, surgical results are not always favorable in cases with thoracic myelopathy due to OPLL and OLF. With respect to thoracic OPLL, a nationwide multicenter prospective study conducted in Japan reported that motor palsy occurred postoperatively in 32.2% of the patients. Several surgical treatments, including laminectomy, extensive cervicothoracic laminoplastic decompression, wide laminectomy with posterior instrumentation, anterior decompression through a posterior approach, lateral rachiotomy, and combined anterior and posterior decompression, have been attempted. The use of instrumentation allows the correction or prevention of kyphosis, thus enhancing and maintaining the decompression effect. With regard to anterior surgery, the sternum splitting approach may be considered in difficult cases. Surgical treatment of thoracic OPLL remains one of the most challenging problems in the field of spine surgery.
| Conclusion|| |
The pathogenesis of OPLL remains unknown, and there is no effective conservative treatment. Surgery is the only option in patients with neurological deficit caused by OPLL. However, several issues remain to be resolved in the future.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]