**1. Introduction**

Ossification of the spinal ligaments impairs spinal mobility and occasionally leads to a spinal disorder [1,2]. Ossification of the posterior longitudinal ligament (OPLL) is common in Asian countries and can cause severe myelopathy [3]. Diffuse idiopathic skeletal hyperostosis (DISH), which is defined as ossification of the anterior longitudinal ligament bridging at least four vertebral segments of the thoracolumbar spine [4,5], has also been recognized as a pathological feature in patients predisposed to ossification and often coincides with the presence of OPLL [6–10]. Although DISH has been widely regarded as an asymptomatic disorder, it is unclear how it affects symptoms related to the whole spine. Few studies have compared patients with and without DISH in terms of clinical symptoms. Therefore, the Japanese Multicenter Research Organization for Ossification of the Spinal Ligament (JOSL), established a nationwide patient registry to prospectively collect the clinical and radiologic data, including whole-spine computed tomography (CT) scans, of OPLL patients. Using data from this registry, this paper focuses on differences in clinical and radiological findings between patients with and without DISH. We further sought to identify any significant associations between clinical symptoms and the severity of DISH in these patients based on patient-reported outcomes.

#### **2. Materials and Methods**

#### *2.1. Patients and Methods*

This multicenter prospective cross-sectional study used data from 16 member institutions of the JOSL established by the Japan Ministry of Health, Labour, and Welfare. The inclusion criteria were as follows: age ≥20 years; diagnosis of cervical OPLL based on radiographic findings; symptoms such as neck pain and upper and/or lower extremity numbness regardless of whether surgery was required, clumsiness, and gait disturbance; a visit made to a participating institution for symptoms between September 2015 and December 2017; and whole-spine CT scans available to determine the location of ossified lesions in the spine. The only exclusion criterion was a history of cervical spine surgery for OPLL. The study was approved by the institutional review board of each participating institution and conducted in accordance with the relevant guidelines and regulations.

#### *2.2. Clinical Evaluation*

Basic demographic and clinical data of patients were collected, including age, sex, diabetes mellitus (DM) status, body mass index (BMI), and presence of neck pain, back pain, and/or low back pain (LBP). Clinical status was evaluated using the following measures: cervical Japanese Orthopaedic Association (JOA) score [11], which is used for functional assessment of patients with cervical myelopathy, JOA Cervical Myelopathy Evaluation Questionnaire (JOA-CMEQ) [12], which assesses the function of the cervical spine, upper and lower extremities, and bladder as well as quality of life; and the JOA Back Pain Evaluation Questionnaire (JOA-BPEQ) [13], which assesses lumbar spine function, social dysfunction, mentality, locomotive function, and body pain. The degree of pain or stiffness in the neck or shoulders, pain or numbness in the arms or hands, and LBP was evaluated using a visual analog scale (VAS).

#### *2.3. Radiologic Evaluations*

CT images of the whole spine were collected for each patient. The images included the cervical, thoracic, and lumbosacral segments, spanning the occipital bone to the sacrum. The incidence of OPLL in the cervical spine from the clivus to C7 and in other spinal regions from T1 to S1 was evaluated on mid-sagittal CT images. Blinded to clinical outcomes, six senior spine surgeons (S.U., K.M., S.M., K.K., N.N., and K.T.) independently evaluated the images, as described previously [13]. OPLL was assessed as DISH if it completely bridged at least four contiguous adjacent vertebral bodies anywhere in the spine based on the criteria established by Resnick and Niwayama [5]. In accordance with a previous report [10], DISH was classified as follows: grade 1, DISH at T3–T10; grade 2, DISH at both T3–10 and C6–T2 and/or T11–L2; and grade 3, DISH extends beyond the C5 and/or L3 levels (Figure 1). To identify any significant differences in clinical findings, we compared patients with and without DISH and those with DISH according to grade. In addition, the ossification of the posterior longitudinal ligament index (OP-index), defined as the number of levels with OPLL in the whole spine [6], was also calculated for each patient.

**Figure 1.** DISH grading system. (**a**) No DISH; (**b**) Grade 1 (bony bridge at T3–T6); (**c**) Grade 2 (T2–T12); (**d**) Grade 3 (C2–L5). DISH, diffuse idiopathic skeletal hyperostosis.
