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Tsukimoto’s first report of ossification of the posterior longitudinal ligament (OPLL) described compression of the spinal cord in the cervical spine secondary to progressive OPLL. Because most studies of OPLL were initially from Japan, OPLL was once termed “the Japanese disease.” However, as more reports from both Eastern and Western countries became available and analyses of case series from other Asian countries increased, it became clear that all contemporary spinal surgeons must be aware of OPLL.
OPLL imposes a unique burden on patients as well as on physicians as compared with cervical spondylotic myelopathy. In patients with a strong tendency to ossification, OPLL can extend all the way from the upper cervical spine down to the lower lumbar spine, with resulting multiple-level severe neural compression ( Fig. 16-1 ). Furthermore, ossification of the dura with resulting spinal cord dysfunction can be common in OPLL and can pose challenges for both the medical treatment and surgical management of this disorder. The purpose of this chapter is to describe the epidemiology, pathophysiology, diagnosis, and treatment of patients with OPLL.
Epidemiology
Prevalence
Morbidity of OPLL in Japan has been reported at 1.9% to 3.2%. Similar or smaller percentages of morbidity in other Asian countries have been reported: 2.1% to 3% in Taiwan, 0.8% to 1.8% in China, 1.5% in the Philippines, 0.95% in Korea, and 0.8% in Singapore. Studies in Europe and the United States have found far less morbidity: 0.1% to 1.3% in the United States, 1.7% in Italy, and 0.1% in Germany. Symptomatic OPLL is speculated to affect 20% to 50% of persons with OPLL, and myelopathic OPLL is found in 29% to 40% of patients with symptomatic OPLL. Cervical OPLL accounts for 70% of all OPLL cases and sometimes accompanies thoracic or lumbar OPLL.
Natural History
Progression of Ossification
Ossification is often found in people who are more than 40 years old. This ossification develops in an axial direction and/or a longitudinal axis. Progression of ossification is more active in younger persons than in older adults. Progression of ossification continues after surgical treatment ( Fig. 16-2 ).
Progression of Neurologic Symptoms
In a large cohort study, 304 patients with no neurologic findings on their first visit were treated conservatively. Myelopathy developed in 55 (17%) of patients with a follow-up of 10 to 30 years, and these patients had a higher range of motion or severe stenosis (>60%) in the cervical spine. Another study observed 21 patients with a small space available for the spinal cord (<12 mm). With a follow-up of 4.2 years on average, only one patient exhibited deteriorated neurologic symptoms, and no patient changed to surgical treatment.
These studies indicate that preventive surgery is not always necessary in patients with slight to mild myelopathy even when compression to the spinal cord is substantial. However, the potential risk of spinal cord injury (SCI), if significant, supports the use of preventive surgery. In a retrospective survey of 453 patients with cervical SCI, Chikuda and colleagues reported that OPLL was found in 106 (23%) patients. OPLL is a significant risk factor for SCI, at least in Japan, after considering the 1.9% to 3.2% prevalence of OPLL. Most (75%) patients with SCI are unaware of their OPLL before injury. As a result, in some countries where asymptomatic OPLL may be highly prevalent in the general population, advocates have proposed instituting a screening program to identify unrecognized OPLL, although it is unclear whether awareness of the disease can actually decrease the incidence of SCI. Regardless, surgeons should educate their patients on the potential risks of SCI associated with incidental falls and other accidental injuries.
Pathophysiology
OPLL is an ectopic ossification. From histologic findings, endochondral ossification forms the majority of ossification, although intramembranous ossification is sometimes observed. Hypertrophy of the posterior longitudinal ligament often precedes ossification. The posterior longitudinal ligament has deep and superficial layers, and ossification usually starts at the attachment of the deep layer to the posterior vertebral body. In some cases, ossification may first develop at the posterior aspect of the vertebral body.
Ossification of the dura, a unique pathologic feature of OPLL, is sometime observed and may result from extension of the bone-forming process with ossification into the neighboring dura. As for the spinal cord, tissue necrosis and cavity formations expand from the central parts of the gray matter to the ventral parts of the posterior column. A triangular deformity of the spinal cord with a less than 60% of normal in more than one segment appeared to be associated with severe and irreversible pathologic changes.
Genetics
Genetic inheritance of OPLL has been validated from various studies. In a nationwide pedigree survey in Japan, 23% of families and 29% of siblings had OPLL among 347 patients. Koga and Sakou and their associates studied the genetics of OPLL. These investigators reported an association between OPLL and some haplotypes in chromosome 6. Following these studies, these investigators performed linkage analysis of 91 sib pairs and found two candidate genes: collagen α2 (XI) ( COL11A2 ) and retinoic X receptor β ( RXRβ ). The former gene, COL11A2, which encodes collagen α2 (XI), a fibril-forming minor collagen of chondrocytes, seems clinically more important. Another team performed a genome-wide linkage study of 142 sib pairs and found an association of COL6A1 and OPLL. Other proposed candidate genes are nucleotide pyrophosphatase (NPPS), bone morphogenetic protein-2 (BMP-2), transforming growth factor-β, B crystalline, cadherin, BMP-4, proteoglycan 1, osteopontin, parathyroid hormone receptor 1, insulin-like growth factor-I, estrogen receptor, and interleukin-1β.
Environmental Factors and Comorbidities
Mechanical stress is regarded as one main cause of progression of ossification. Mechanical stress increases production of various proteins and cytokines such as alkaline phosphatase, BMPs, and osteopontin at the site of ossification.
Diabetes is associated with OPLL. Insulin-like growth factor-I and insulin receptors are suspected to play a key role in the formation of OPLL. Akune and colleagues showed that the insulin secretory response was associated with the extent of OPLL ligament. Hypoparathyroidism and hypophosphatemic rickets are also factors in OPLL.
Diagnosis
Imaging
Cervical OPLL is categorized into four groups from lateral radiographs: the continuous type, the mixed type, the segmental type, and the localized type ( Fig. 16-3 ). One type of OPLL can develop into another after elongation or fusion of ossification. The continuous type and the mixed type have common properties, and they are often regarded as a single group. Genetic study also validated this affinity between a continuous type and a mixed type.
The accuracy of the radiographic classification is not high because ossification is often fuzzy. Computed tomography (CT) is the best imaging modality to evaluate the ossification. The presence of a double layer of ossification called the “double-layer sign” usually indicates ossification of the dura ( Fig. 16-4 ). Identification of ossification of the dura is important because resection of the ossification can result in cerebrospinal fluid leaks during anterior decompressions. Although not necessary, reconstructed three-dimensional CT images may demonstrate the ossification more intuitively ( Fig. 16-5 ).
