Ossification of the spinal ligaments is a group of disease, characterized by heterotopic ossification or calcification in the tissues of the spinal ligaments. Among them, ossification of the ligamentum flavum (OLF) is rarely observed, particularly in the cervical spine. Liang et al.[5] reviewed the CT data for 2000 patients with the whole-spine images and reported that the prevalence of OLF in the cervical spine was 0.25%. And the condition is more likely to affects the East Asians, especially in Japanese and Chinese population.
In clinical practice, CLF and OLF are often confused because of inadequate histological examination. CLF and OLF are rare entities that have similarities in their clinical features and treatments, but the two conditions of calcification and ossification significantly differ in pathological mechanism and neuroradiologic appearances[3]. Calcification is characterized by deposition of calcium or salt-related compounds in soft tissue, while ossification refers to the abnormal formation of mature trabecular bone. Radiologically, CLF is usually demonstrated on cervical CT as an non-contiguous, oval-shaped mass, located at the posterolateral part of the lamina, which is involved in crystal deposits. Unlike calcification, ossified lesion is more irregular, and usually shows V-shaped high density masses along the lamina[6]. In addition, previous reports have identified that CLF occurs predominantly in the lower part of the cervical spine, whereas OLF was usually distributed in the upper or lower thoracic region[6]. Cervical CT scan was performed on all patients of our study, the lesion was oval in shape, non-contiguous, adhered ventrally to the lamina. The pathological results of six cases revealed degenerative ligamentum flavum with dark blue calcifications, which were consistent with those of CPPD diseases.
In 1976, Nanko et al.[7] reported the first case of symptomatic calcification of the ligamentum flavum in the cervical spine. In 1980, Kawano et al.[8] reported one case with cervical radiculomyelopathy due to CPPD in the ligamenta flava. Since then, many reports of this conditon followed. The exact pathophysiology of CLF is largely unknown; however, it involves accumulation of calcium pyrophosphate dehydrate crystals[9]. CPPD, also known as pyrophosphate arthropathy or pseudogout, is defined by the accumulation of CPPD crystal in articular and periarticular tissues. The disease predominantly affects the peripheral joints, but may also concern spine[10]. The cervical region is the most commonly affected site within the spine followed by the thoracic and lumbar spine. Aging is a major risk factor for the development of CPPD crystal-associated arthritis, and CLF predominantly affects elderly women[3, 6, 10]. Baba, et al.[11] published a 8 cases series along with a review of 91 reports of CLF. Of all, 85% were female with an average age of 64.8 years. In our study, the male: female ratio was 1:6 and the mean age was 70.6 years, which is consistent with previous reports. It has been postulated that decreased estrogen levels at old age may be partially responsible for higher incidence of CLF in females compared to male.
Periodontoid calcification is a radiological signs defined by the radiographic calcifications in a crown-like configuration around the odontoid process, which is usually detected by CT scans. Calcifification can develop anywhere around the odontoid process, whereas it tended to be usually located in the transverse ligament of the atlas (TLA)[12]. Calcified lesion around the odontoid process caused by CPPD disease is a cause of acute inflammatory neck pain and stiffness, which is typically known as the crowned dens syndrome[13] (CDSyn). However, calcification is not always symptomatic. Sano et al.[14] reported that the prevalence of CDSyn in patients with periodontoid calcification was 12.5% (11/88). Based on the analysis of our own experience and of the published literature, the calcifications surrounding the odontoid process without clinical symptoms were definded as crowned dens sign (CDSign) in our study. In 2016, Kobayashi et al.[15] reported one patient with acute neck pain caused by calcified cervical yellow ligament combined with periodontoid calcification. Later, Chang et al.[16] and Lee et al.[17] reported the cases of cervical myelopathy caused by calcification of the ligamentum flavum of the cervical spine with asymptomatic CDSyn, respectively. The coexistence of CLF and CDSign is an extremely rare event, only three similar cases have been reported in the English-language literature. It seems that either association of CDSign and CLF is a rare entity or it is a coincidence. In our study, twenty-six patients with both CLF and CDSign were the main focus of this study, and the CDSign was identified in 79% (26 of 33) of the patients with CLF. Lu et al.[6] reported that 72%(13/18) of patients had periodontoid calcifcations in patients with calcifcations of cervical ligamentum favum due to CPPD deposition. Thus, the coexistence of two diseases is unlikely to be fortuitous. We found that it is more than half of cases with CLF and concurrent CDSign overlap syndrome in our study, it mightly suggest the association of these two conditions is stronger than a coincidence. On the basis of literature review, Muthukumar et al.[18] found two types of CPPD crystal deposition in the cervical spine: calcifications of the ligamenta flava in the subaxial cervical spine (Type 1) and periodontoid calcifications in the upper cervical spine(Type 2). The exact relation between these entities is not known, but the relatively frequent association among these rare diseases suggests that there may be a pathophysiological relationship among them and not only a simple coincidence. In our opinion, CLF combined with CDSign may be a rare form of the cervical manifestation of CPPD disease, rather than a coincidence.
Clinical manifestations of patients with CLF are diverse, most cases presented with radiculomyelopathy, some patients can be completely asymptomatic. The primary symptoms of CDSyn are acute inflammatory neck pain and neck stiffness. In our study, 22 patients reported axial neck pain, 11 patients had radicular symptoms, 19 patients had myelopathy. Coexistent CDSign was observed in 26 patients, however, which may not affect clinical outcome in the treatment of CLF. In addition, there is a high incidence of cervical spondylosis among the patients with CLF of our study. Posterior cervical spine surgery is a common surgical technique used to treat a variety of cervical spine disorders. Yang J et al.[19] reported 15 cases of cervical myelopathy caused by OLF, all patients underwent bilateral laminectomy, and achieved satisfactory clinical results. Finally, in our study, 23 patients underwent posterior surgery, 8 patients received anterior surgery, and 2 patients received conservative treatment. The surgery went well with a satisfactory result. In our opinion, anterior decompression surgery is effective in the treatment of patients with severe disc herniation and CLF.