Imaging Features of Early Diffuse Idiopathic Skeletal Hyperostosis (pre-DISH): Analysis of Progression of Ligament Ossification over 5 Years by Computed Tomography.

Introduction: Some patients who have not been diagnosed with diffuse idiopathic skeletal hyperostosis (DISH) (patients in the preclinical stage of DISH [pre-DISH]) may develop DISH in the future. However, there are currently no clearly defined diagnostic criteria for pre-DISH. This study aims to define pre-DISH by analyzing the change in the ossification extent in each intervertebral space in the thoracic and lumbar spines over time using computed tomography (CT). Methods: Of the patients who underwent CT of the thoracic to pelvic region at least twice from 2009 to 2018, 188 who underwent CT at an interval of 5 years to 5 years and 2 months were enrolled. The prevalence of DISH during the first and second CT scans was investigated. The pre-DISH feature was defined, and the prevalence of pre-DISH on the first CT and the change after 5 years in patients with pre-DISH was investigated. Results: Of the 188 patients, 37 (19.7%) and 48 (25.5%) were diagnosed with DISH on the first and second CT scans, respectively. Pre-DISH was defined as the ossification characterized by the modified Mata score of three contiguous intervertebral spaces with a score of ≥2 points (222; 2 points, ligament ossification of half or more of the intervertebral disc height but incomplete fusion), and 52 patients were diagnosed with pre-DISH. Of the 52 patients with a score of ≥(222), 11 (21.2%) were diagnosed with DISH 5 years later. Conclusions: Patients who have three contiguous intervertebral spaces with a modified Mata score of 2 or 3 points should be considered pre-DISH.

Hemodynamic deterioration due to increased anterior and posterior cardiac compression during posterior spinal fusion for scoliosis with pectus excavatum.

Hemodynamics may deteriorate during the perioperative period when performing posterior spinal fusion in patients with pectus excavatum and scoliosis. A 13-year-old teenager diagnosed with Marfan syndrome had thoracic scoliosis and pectus excavatum. Thoracic scoliosis was convex to the right, and a right ventricular inflow tract stenosis was observed due to compression induced by the depressed sternum. The patient underwent T3-L4 posterior spinal fusion surgery for scoliosis. Deterioration of hemodynamics was observed when the patient was placed in the prone position or when the thoracic spine was corrected to the left front. Postoperative computed tomography examination showed that the mediastinal space was narrowed due to the corrected thoracic spine. Special attention should be paid in the following cases: (1) severe pectus excavatum, (2) right ventricular inflow tract compression due to depressed sternum on the left side, (3) correction of the thoracic spine on the left front, (4) long-term surgery, and (5) risk of massive bleeding. In some cases, pectus excavatum surgery should be prioritized.

Serum lactate dehydrogenase levels predict the prognosis of patients with soft tissue sarcoma.

Several studies have reported the prognostic factors for soft tissue sarcoma. Although serum lactate dehydrogenase (LDH) levels are associated with poor prognosis in several types of cancer, their role in soft tissue sarcomas remains unclear. Therefore, the present study evaluated the association between serum LDH levels and the clinical characteristics and prognosis of soft tissue sarcoma. A total of 103 patients diagnosed with primary soft tissue sarcoma between 2003 and 2019 were retrospectively examined, and the association between serum LDH levels at the first visit and clinical characteristics were analysed. In high-grade soft tissue sarcoma, the association between survival and clinical characteristics, including stratified LDH levels, was also analysed. Serum LDH levels were stratified (>253 and ≤253 IU/l) according to the standard values used at our institution. High serum LDH levels were significantly associated with the presence of metastasis and histological grade (P<0.001 and 0.040, respectively). In both the univariate and multivariate analyses, disease-specific survival (DSS) was significantly worse in patients with high-grade soft tissue sarcoma and high serum LDH levels than in patients with normal serum LDH levels (univariate analysis: P=0.025; multivariate analysis: Hazard ratio, 4.60; 95% confidence interval, 1.16-18.2; P=0.030). In conclusion, high serum LDH levels at the first visit predicted the presence of distant metastasis, high histological grade and worse DSS in patients with high-grade soft tissue sarcoma. Therefore, in patients with high serum LDH levels at the first visit, these risks should be considered during pretreatment examinations and post-treatment follow-up.

Thoracic spondylotic myelopathy presumably caused by diffuse idiopathic skeletal hyperostosis in a patient who underwent decompression and percutaneous pedicle screw fixation.

A 74-year-old man developed bilateral lower limb spastic paresis. He was diagnosed with thoracic spondylotic myelopathy presumably caused by mechanical stress that was generated in the intervertebral space (T1-T2) between a vertebral bone bridge (C5-T1) due to diffuse idiopathic skeletal hyperostosis after anterior fixation of the lower cervical spine and a vertebral bone bridge (T2-T7) due to diffuse idiopathic skeletal hyperostosis in the upper thoracic spine. Treatment included posterior decompression (T1-T2 laminectomy) and percutaneous pedicle screw fixation at the C7-T4 level. Six months after surgery, the patient could walk with a cane, and the vertebral bodies T1-T2 were bridged without bone grafting. For thoracic spondylotic myelopathy associated with diffuse idiopathic skeletal hyperostosis, decompression and percutaneous pedicle screw fixation are effective therapies.

Diffuse idiopathic skeletal hyperostosis: A potential factor in the induction of thoracic spondylotic myelopathy.

BACKGROUND: Thoracic spondylotic myelopathy (TSM) commonly occurs at the thoracolumbar junction, and mechanical stress is thought to be involved. In DISH, the anterior longitudinal ligament becomes ossified. Although DISH is suspected to be involved in TSM pathology, reports are limited. Aim of this study is to investigate the association between (TSM) and diffuse idiopathic skeletal hyperostosis (DISH). METHODS: Fifty-one patients with thoracic myelopathy underwent surgery between April 2008 and April 2017. Of these, 28 patients with TSM were included and examined. DISH was confirmed using computed tomography (CT). Subjects were divided into DISH and non-DISH sub-groups according to CT findings, and the DISH coexistence rate was calculated. Groups were analyzed for sex, age, postoperative Japanese Orthopedic Association (JOA) score, and reoperation status. In the DISH group, the positional relationship between the affected vertebral level of TSM and consecutive vertebral bone bridges was analyzed. Patients without spinal disease matched for sex and age were enrolled as controls (N = 56). The DISH coexistence rate was compared and analyzed between groups. RESULTS: Mean age at surgery was 67.8 years (43-82 years; 22 men, 6 women). DISH was detected in 17 of 28 patients (60.7%; 15 men, 2 women). No significant difference in the improvement rate of JOA score was observed between groups. TSM occurred at: lower border of a consecutive vertebral bone bridge, N = 4; upper border, N = 3; between consecutive vertebral bone bridges, N = 5; one vertebral body away from a consecutive vertebral bone bridge, N = 5. No patient had TSM occurring within a consecutive vertebral bone bridge. The DISH coexistence rate in patients with TSM (60.7%) was significantly higher than that in controls (20/56, 35.7%) (p = 0.03). CONCLUSION: Mechanical stress caused by consecutive vertebral bone bridges due to DISH may be involved in TSM pathogenesis. Therefore, in DISH patients, attention needs to be paid to TSM onset.

Association Between Vertebral Fracture and Diffuse Idiopathic Skeletal Hyperostosis.

STUDY DESIGN: Retrospective case-control study. OBJECTIVE: To investigate the prevalence and characteristics of diffuse idiopathic skeletal hyperostosis (DISH) in vertebral fracture patients admitted to our hospital. SUMMARY OF BACKGROUND DATA: Although vertebral fracture is generally treated conservatively with rest and use of a corset, surgery with rigid internal fixation is recommended for vertebral fractures in patients with DISH. Thus, treatment strategies for vertebral fracture differ according to the presence or absence of DISH. However, only a few studies have investigated the prevalence of DISH in vertebral fracture patients. METHODS: A total of 159 patients (49 men and 110 women, with a mean age of 82.9 years) who were diagnosed with fresh vertebral fracture and required admission to HITO Hospital. The diagnosis of fresh vertebral fracture was made using x-ray imaging, computed tomography, and magnetic resonance imaging, and the presence or absence of DISH was assessed. In addition, age, sex, bone mineral density ( % young adult mean), blood test results, treatment, and length of hospital stay were compared between patients with and without DISH. RESULTS: The proportion of patients with DISH among the patients with vertebral fracture was 33.9% (54 of 159 patients). The proportions in men and women were 38.8% and 31.8%, respectively, with no significant difference between sexes (P = 0.39). The patients in the DISH group were older than those in the non-DISH group (83.6 vs. 79.4 years, P = 0.009), and the DISH group had higher glycated hemoglobin A1c (P = 0.005), higher bone mineral density (P = 0.042), and longer length of hospital stay (P = 0.0001) compared with those in the non-DISH group. CONCLUSION: The proportion of patients with DISH among the vertebral fracture patients was 33.9%. Given that patients with DISH may require different treatment approaches, careful observation is needed. LEVEL OF EVIDENCE: 3.

Risk Factors for Delirium after Spine Surgery: An Age-Matched Analysis.

STUDY DESIGN: A retrospective cohort study. PURPOSE: To investigate the risk factors for postoperative delirium after spine surgery, excluding older age, which has already been established as a strong risk factor. OVERVIEW OF LITERATURE: More than 30 risk factors have been reported for delirium after spine surgery, making it challenging to identify which factors should be prioritized. We hypothesized that risk factors could not be prioritized to date because the factor of older age is very strong and influenced other factors. To eliminate the influence of older age, we performed an age-matched group comparison analysis for the investigation of other risk factors. METHODS: This study involved 532 patients who underwent spine surgery. Two patients of the same age without delirium (delirium negative group) were matched to each patient with delirium (delirium positive group). Differences in suspected risk factors for postoperative delirium between the two groups identified from previous reports were analyzed using univariate analysis. Multivariate analysis was performed for factors that showed a significant difference between the two groups in the univariate analysis. RESULTS: Fifty-nine (11.1%) of 532 patients developed postoperative delirium after spine surgery. Large amounts of intraoperative bleeding, low preoperative concentration of serum Na, high postoperative (day after surgery) serum level of C-reactive protein, low hematocrit level, low concentration of albumin, and high body temperature were detected as significant risk factors in the univariate analysis. Large amounts of intraoperative bleeding remained a risk factor for postoperative delirium in the multivariate analysis. CONCLUSIONS: We should pay attention to and take precautions against the occurrence of postoperative delirium after spine surgery in patients of older age or those who experience severe intraoperative bleeding.

Altered Gene Expression of RNF34 and PACAP Possibly Involved in Mechanism of Exercise-Induced Analgesia for Neuropathic Pain in Rats.

Despite the availability of several modalities of treatment, including surgery, pharmacological agents, and nerve blocks, neuropathic pain is often unresponsive and sometimes progresses to intractable chronic pain. Although exercise therapy is a candidate for treatment of neuropathic pain, the mechanism underlying its efficacy has not been elucidated. To clarify the molecular mechanism for pain relief induced by exercise, we measured Rnf34 and Pacap mRNA levels in the spinal cord dorsal horn of SNL rats, a model of neuropathic pain. SNL model rats exhibited stable mechanical hyperalgesia for at least 6 weeks. When the rats were forced to exercise on a treadmill, mechanical and thermal hyperalgesia were significantly ameliorated compared with the non-exercise group. Accordingly, gene expression level of Rnf34 and Pacap were also significantly altered in the time course analysis after surgery. These results suggest that exercise therapy possibly involves pain relief in SNL rats by suppressing Rnf34 and Pacap expression in the spinal cord.

Spinal fusion in a patient with Fukuyama congenital muscular dystrophy.

Many studies have evaluated surgical treatments for spinal deformities in patients with neuromuscular disease. However, few reports have described patients with Fukuyama congenital muscular dystrophy (FCMD). A 13-year-old boy with FCMD was unable to sit for long periods or sleep in the supine position because of progressive scoliosis. His Cobb angle worsened from 27° to 41° in 5months. He underwent standard posterior spinal fusion and pedicle-screw-alone fixation from T5 to S1. Postoperatively, his Cobb angle improved from 41° to 25° without exacerbation for 2years. After the surgery, he was able to sit for longer periods without pain, and he and his family were satisfied with the efficacy of the spinal fusion. Some patients with mild FCMD can sit at the age of puberty, but progression to scoliosis is possible. Therefore, spinal fusion for progressive scoliosis in patients with FCMD should be considered.

Eight years of follow-up after laminectomy of calcium pyrophosphate crystal deposition in the cervical yellow ligament of patient with Coffin-Lowry syndrome: A case report.

BACKGROUND: We report 8 years of follow-up after decompression to treat cervical myelopathy in a patient with Coffin-Lowry syndrome (CLS). CLS is a rare X-linked semidominant syndrome associated with growth and psychomotor retardation, general hypotonia, and skeletal abnormalities. In this patient, the spinal cord was compressed by calcium pyrophosphate crystal deposition in the cervical yellow ligament (YL). To date, only 1 report has described clinical features after surgery for calcified cervical YL in CLS. METHODS: A 15-year-old male with tetraplegia secondary to compression of the cervical spinal cord induced by a hypoplastic posterior arch of C1 and calcification of the YL from C2 to C7 was treated surgically with laminectomy from C1 to C7. The patient's history, clinical examination, imaging findings, and treatment are reported. The patient was incapable of speech because of mental retardation, so he could not describe his symptoms. Gait disturbance worsened over the 2 months before admission to our hospital. At admission, the patient could not move his extremities, and tendon reflexes of the upper and lower extremities were significantly increased. Computed tomography of the cervical spine showed YL calcification from C2 to C7. Magnetic resonance imaging showed consecutive compression of the cervical spinal cord. We diagnosed quadriplegia secondary to cervical cord damage and performed emergency surgery. RESULTS: During C1-C7 laminectomy, YL calcification in C2-C7 was observed. The calcification was confirmed as calcium pyrophosphate by crystal analysis. Quadriplegia gradually resolved, and almost disappeared by 2 weeks after the operation. Cervical hyperlordosis was observed in radiographs starting from 1 month after the operation, but it has not progressed and is not associated with any symptoms. CONCLUSIONS: The efficacy of decompression continued, and no postoperative complications have occurred during at least 8 years of follow-up.

Different analgesic effects of adenosine between postoperative and neuropathic pain.

BACKGROUND: Adenosine is an endogenous neuromodulator in both the peripheral and central nervous systems. Adenosine inhibits pain signals by hyperpolarizing neuronal membrane. METHODS: To clarify the effects of adenosine on pain signals, we tested intrathecal adenosine injection in two neuropathic pains (spinal cord compression and chronic constriction of sciatic nerve) and postoperative pain (plantar incision). RESULTS: In all three kinds of pain models, significant shortening of withdrawal latencies to thermal stimulation were detected from 24 h to 1 week after the surgery. Significant improvements of pain sensation were observed in all three models after intrathecal injection of Cl-adenosine 24 h after surgery. At 72 h after surgery, intrathecal Cl-adenosine injection inhibited hyperalgesia in the two neuropathic pain models but not in the postoperative pain model. Adenosine A1R messenger RNA (mRNA) expression significantly decreased in the plantar incision model. Adenosine A1R protein levels also decreased compared with the other two models and normal control. CONCLUSIONS: These results suggest that adenosine effectively inhibits pain signals in neuropathic pain but is less effective in postoperative pain because of the decrease in adenosine A1 receptors.

3-D MRI/CT fusion imaging of the lumbar spine.

OBJECTIVE: The objective was to demonstrate the feasibility of MRI/CT fusion in demonstrating lumbar nerve root compromise. MATERIALS AND METHODS: We combined 3-dimensional (3-D) computed tomography (CT) imaging of bone with 3-D magnetic resonance imaging (MRI) of neural architecture (cauda equina and nerve roots) for two patients using VirtualPlace software. RESULTS: Although the pathological condition of nerve roots could not be assessed using MRI, myelography or CT myelography, 3-D MRI/CT fusion imaging enabled unambiguous, 3-D confirmation of the pathological state and courses of nerve roots, both inside and outside the foraminal arch, as well as thickening of the ligamentum flavum and the locations, forms and numbers of dorsal root ganglia. Positional relationships between intervertebral discs or bony spurs and nerve roots could also be depicted. CONCLUSION: Use of 3-D MRI/CT fusion imaging for the lumbar vertebral region successfully revealed the relationship between bone construction (bones, intervertebral joints, and intervertebral disks) and neural architecture (cauda equina and nerve roots) on a single film, three-dimensionally and in color. Such images may be useful in elucidating complex neurological conditions such as degenerative lumbar scoliosis(DLS), as well as in diagnosis and the planning of minimally invasive surgery.

Intrathecal transplantation of autologous macrophages genetically modified to secrete proenkephalin ameliorated hyperalgesia and allodynia following peripheral nerve injury in rats.

To develop a novel genetic approach for the treatment of pain, we tested the transplantation of gene-transferred autologous macrophages by lumbar puncture. A rat neuropathic pain model was produced by chronic constriction of the sciatic nerve. Autologous macrophages were collected from the intraperitoneal space. Then human proenkephalin gene was transferred into the macrophages by electroporation. The gene-transferred macrophages were transplanted into the subarachnoid space by lumbar puncture. One week after transplantation, the heat hyperalgesia and allodynia induced by sciatic nerve constriction completely remitted. The analgesic action continued until at least 4 weeks after transplantation. The transplanted macrophages migrated into the spinal cord and expressed proenkephalin mRNA and Met-enkephalin protein. The method we tested in the present study may be a safe, simple and effective way to inhibit pain sensation after peripheral nerve injuries.

Resolution of intraspinal retro-odontoid cyst associated with os odontoideum after posterior fixation.

STUDY DESIGN: A case report and review of previous literature. OBJECTIVES: To describe the diagnosis and successful treatment of an intraspinal retro-odontoid cyst associated with an os odontoideum. SUMMARY OF BACKGROUND DATA: Retro-odontoid cysts associated with atlantoaxial instability are extremely rare. Direct excision of the cysts has commonly been performed for the surgical treatment of myelopathy. METHODS: A retro-odontoid cyst in a 58-year-old woman with os odontoideum was treated surgically by posterior fixation between C1 and C3 without resection of the retro-odontoid mass. The patient's history, clinical examination, imaging findings, and treatment are reported. RESULTS: The patient experienced walking difficulty, numbness in the upper and lower limbs, and hypesthesia in both hands. Congenital C2/3 fusion and atlantoaxial instability associated with an os odontoideum were found in the radiographs. Magnetic resonance imaging detected a round retro-odontoid mass, which compressed the spinal cord. The mass showed uniform low intensity on T1-weighted images and uniform high signal intensity on T2-weighted images. Gadolinium-diethylenetriaminepenta-acetic acid-enhanced T1-weighted images showed rim enhancement of the mass with no internal enhancement. Three months after the operation, the mass was no longer visible in a magnetic resonance imaging examination and the patient completely recovered motor function in her extremities. CONCLUSIONS: Posterior fixation without resection was successfully used to eliminate a retro-odontoid cyst associated with atlantoaxial instability.

A periosteal chondroma in the lumbar spinal canal. Case report.

Periosteal chondromas located in the spine are rare. The authors document a case of periosteal chondroma in the lumbar spinal canal of a 77-year-old man. The patient had severe pain in his right leg and used a wheelchair because of weakness in both legs. Magnetic resonance imaging revealed a round tumor that was hypo- or isointense on T1-weighted images and uniformly hyperintense on T2-weighted images. Administration of gadolinium-diethylenetriamine pentaacetic acid resulted in margin enhancement on T1-weighted images. During the operation, a round tumor 1.5 cm in diameter was found on the surface of the anterior wall of the L-3 lamina. Histological examination revealed that the tumor consisted of chondroid tissue with typical chondrocytes, indicating that it was a periosteal chondroma.

Adenosine triphosphate inhibits cytokine release from lipopolysaccharide-activated microglia via P2y receptors.

Microglial proliferation and activation have been reported to occur after several central nervous system injuries. In this study, we tested the effects of adenosine triphosphate (ATP) on cultured microglia obtained from the spinal cord of rat embryos. The amounts of tumor necrosis factor alpha (TNF-alpha), interleukin 1beta and interleukin 6 released from the microglia, which were stimulated by lipopolysaccharide (LPS; 100 ng/ml), were inhibited by the simultaneous addition of ATP in a dose dependent manner (10-300 microM). We examined the effect of several endogenous purines (ATP, ADP, CTP, UDP, UTP) and P(2)y receptor agonists (ADPbetaS and 2-methylthio-ATP) on LPS-induced TNF-alpha release. The rank order of inhibitory potency of endogenous purines on TNF-alpha release was: ATP>ADP>>UTP>UDP>CTP. The latter three were much less potent than the former two. The addition of 10 microM 2-methylthio-ATP showed a potency similar to 100 microM ATP. The addition of ADPbetaS, however, showed less effect. These endogenous purines and selective ATP receptor agonists showed a similar inhibitory effect in their rank order on LPS-induced interleukin 6 release. We demonstrate that ATP inhibits cytokine release from LPS-activated microglia via metabotropic receptors. The application of P(2)y receptor agonists might be considered as a pharmacological treatment of several pathological conditions of the spinal cord, including toxic immunoreactions.

Prostaglandin E1 analog inhibits the microglia function: suppression of lipopolysaccharide-induced nitric oxide and TNF-alpha release.

Release of nitric oxide and TNF-alpha, a toxic cytokine, have been reported to accelerate neuronal damage under several pathological conditions, such as trauma or ischemia in the central nervous system. In the present study, we tested the effect of alprostadil alfadex, a prostaglandin E1 analog, on cultured microglia from the rat spinal cord. The cultured microglia were exposed to lipopolysaccharide (LPS) (100 ng/ml), an endotoxin, for 24 h, then the released nitric oxide and TNF-alpha in the culture media was analyzed. The released nitric oxide was detected by the Griess reaction and released TNF-alpha was measured using ELISA method. The LPS-induced nitric oxide release was inhibited by the simultaneous addition of alprostadil alfadex in a dose-dependent manner (0.1-100 microM). The LPS-induced TNF-alpha release was also inhibited by alprostadil alfadex addition (0.1-100 microM). The IC50 values of alprostadil alfadex on nitric oxide and TNF-alpha release were about 1 and 10 microM, respectively. These results suggest that prostaglandin E1 possibly protects spinal cord neurons from several types of neurodegenerative damage, not only via increased blood supply, but also via inhibition of pathological immunoreactions of activated microglia.