Magnetic resonance imaging assessment of degenerative cervical myelopathy: a review of structural changes and measurement techniques.

Degenerative cervical myelopathy encompasses a spectrum of age-related structural changes of the cervical spine that result in static and dynamic injury to the spinal cord and collectively represent the most common cause of myelopathy in adults. Although cervical myelopathy is determined clinically, the diagnosis requires confirmation via imaging, and MRI is the preferred modality. Because of the heterogeneity of the condition and evolution of MRI technology, multiple techniques have been developed over the years in an attempt to quantify the degree of baseline severity and potential for neurological recovery. In this review, these techniques are categorized anatomically into those that focus on bone, ligaments, discs, and the spinal cord. In addition, measurements for the cervical spine canal size and sagittal alignment are also described briefly. These tools have resulted collectively in the identification of numerous useful parameters. However, the development of multiple techniques for assessing the same feature, such as cord compression, has also resulted in a number of challenges, including introducing ambiguity in terms of which methods to use and hindering effective comparisons of analysis in the literature. In addition, newer techniques that use advanced MRI are emerging and providing exciting new tools for assessing the spinal cord in patients with degenerative cervical myelopathy.

Spontaneous regression and near disappearance of a calcified herniated thoracic disc in a 44-year-old male: illustrative case.

BACKGROUND: Herniation of an intervertebral disc (IVD) is found predominantly in the lumbar and cervical spine of both children and adults, but herniated IVDs of the thoracic spine are a rare occurrence. However, approximately 40% of herniated thoracic disc cases are calcified. Approximately 0.65% of all spinal herniations are calcified herniated thoracic discs (CHTDs). CHTDs can be treated conservatively or invasively, depending on the symptoms and degree of neurological deficit present. OBSERVATIONS: The authors report a 44-year-old male with near complete reabsorption and disappearance of a CHTD. A review of the available literature indicates that there are only seven adult patients in whom this phenomenon has been reported. LESSONS: Determining the best form of invasive treatment is a challenge for surgeons given the complexity of this condition. While the disappearance of calcified herniated discs of the lumbar and cervical spine has been reported, reports of the regression of CHTDs are rare. The disappearance of CHTDs is more commonly reported in children who undergo conservative treatment, while surgery is reserved for children who experience progressive pain and neurological deficit. Given the success of conservative treatment of CHTDs in children, conservative treatment methods should be considered when treating mildly symptomatic adults.

Three-dimensional architecture of the neurovascular and adipose zones of the upper and lower lumbar intervertebral foramina: an epoxy sheet plastination study.

OBJECTIVE: Kambin's triangle and the safe triangle are common posterolateral approaches for lumbar transforaminal endoscopic surgery and epidural injection. To date, no consensus has been reached on the optimal transforaminal approach, in particular its underlying anatomical mechanism. The aim of this study was to investigate the 3D architecture of the neurovascular and adipose zones in the upper and lower lumbar intervertebral foramina (IVFs). METHODS: Using the epoxy sheet plastination technology, 22 cadaveric lumbar spines (12 female and 10 male, age range 46-89 years) were prepared as a series of transverse (11 sets), sagittal (8 sets), and coronal (3 sets) slices with a thickness of 0.25 mm (6 sets) or 2.5 mm (16 sets). The high-resolution images of the slices were scanned and analyzed. The height, area, and volume of 30 IVFs from T12-L1 to L4-5 were estimated and compared. This study was performed in accord with the authors' institutional ethical guidelines and approved by the institutional ethics committees. RESULTS: The findings were as follows. 1) The 3D boundaries of the lumbar IVF and its subdivisions were precisely defined. 2) The 3D configuration of the neurovascular and adipose zones was different between the upper and lower lumbar IVFs; zoning in the upper lumbar IVFs was much more complex than that in the lower lumbar IVFs. 3) In general, the infraneural adipose zone gradually tapered and rotated from the inferoposterolateral aspect to the superoanteromedial aspect. 4) The average height, area, and volume of the IVF gradually increased from the upper to the lower lumbar spine. Within a lumbar IVF, the volumes below and above the inferior border of the dorsal root ganglia were similar. CONCLUSIONS: This study highlights differences of fine 3D architecture of neurovascular and adipose tissues between the upper and lower lumbar IVFs, with related effects on the transforaminal approaches. The findings may contribute to optimization of the surgical approaches to and through the IVF at different lumbar spinal levels and also may help to shorten the learning curve for the transforminal techniques.

Induction of proinflammatory cytokine production in intervertebral disc cells by macrophage-like THP-1 cells requires mitogen-activated protein kinase activity.

OBJECTIVE: To determine the role played by mitogen-activated protein kinase (MAPK) signaling in the interactions between macrophages and intervertebral disc (IVD) cells, it was hypothesized that MAPK inhibition would modulate the production of the proinflammatory cytokines associated with inflammatory reaction in IVD cells. METHODS: Human annulus fibrosus (AF) and nucleus pulposus (NP) cells were cocultured with phorbol myristate acetate-stimulated macrophage-like THP-1 cells, with and without SB202190 (a p38-α and -ß inhibitor), SP600125 (a c-Jun N-terminal kinase [JNK] inhibitor), and PD98059 (an extracellular signal-regulated kinase [ERK] 1/2 inhibitor). The cytokines in conditioned media from cocultured and macrophage-exposed (nemotic) cells were assayed using enzyme-linked immunosorbent assays (ELISAs). RESULTS: Interleukin (IL)-6 and IL-8 were secreted in greater quantities by the cocultured cells compared with naive IVD cells and macrophages (MΦ) cultured alone. The tumor necrosis factor (TNF)- α and IL-6 levels produced by the NP cells cocultured with MΦs (NP-MΦ) were significantly lower than those produced by AF cells cocultured with MΦs (AF-MΦ). SB202190 dose-dependently suppressed IL-6 secretion by AF-MΦ and NP-MΦ cocultures, and 10 µM SB202190 significantly decreased IL-6 and IL-8 production in nemotic AF and NP pellets. SP600125 at 10 µM significantly suppressed the production of TNF α IL-6. and IL-8 in AF-MΦ and NP-MΦ cocultures and significantly suppressed IL-1ß production in the NP-MΦ coculture. Administration of 10 µM PD98059 significantly decreased IL-6 levels in the AF-MΦ coculture, and decreased the levels of TNF α and IL-8 in both the AF-MΦ and NP-MΦ cocultures. CONCLUSIONS: The present study shows that inhibitors of p38 MAPK effectively controlled IL-6 production during inflammatory reactions and that JNK and ERK1/2 inhibitors successfully suppressed the production of major proinflammatory cytokines during interactions between macrophages and IVD cells. Therefore, selective blockade of these signals may serve as a therapeutic approach to symptomatic IVD degeneration.

Morphometric analysis of the developing pediatric cervical spine.

OBJECTIVE Our understanding of pediatric cervical spine development remains incomplete. The purpose of this analysis was to quantitatively define cervical spine growth in a population of children with normal CT scans. METHODS A total of 1458 children older than 1 year and younger than 18 years of age who had undergone a cervical spine CT scan at the authors' institution were identified. Subjects were separated by sex and age (in years) into 34 groups. Following this assignment, subjects within each group were randomly selected for inclusion until a target of 15 subjects in each group had been measured. Linear measurements were performed on the midsagittal image of the cervical spine. Twenty-three unique measurements were obtained for each subject. RESULTS Data showed that normal vertical growth of the pediatric cervical spine continues up to 18 years of age in boys and 14 years of age in girls. Approximately 75% of the vertical growth occurs throughout the subaxial spine and 25% occurs across the craniovertebral region. The C-2 body is the largest single-segment contributor to vertical growth, but the subaxial vertebral bodies and disc spaces also contribute. Overall vertical growth of the cervical spine throughout childhood is dependent on individual vertebral body growth as well as vertical growth of the disc spaces. The majority of spinal canal diameter growth occurs by 4 years of age. CONCLUSIONS The authors' morphometric analyses establish parameters for normal pediatric cervical spine growth up to 18 years of age. These data should be considered when evaluating children for potential surgical intervention and provide a basis of comparison for studies investigating the effects of cervical spine instrumentation and fusion on subsequent growth.

Effects of vertebroplasty on endplate subsidence in elderly female spines.

OBJECT: The aim in this study was to quantify the effects of vertebroplasty on endplate subsidence in treated and adjacent vertebrae and their relationship to endplate thickness and underlying trabecular bone in elderly female spines. METHODS: Vertebral compression fractures were created in female cadaveric (age range 51-88 years) thoracolumbar spine segments. Specimens were placed into either the control or vertebroplasty group (n = 9/group) such that bone mineral density, trabecular microarchitecture, and age were statistically similar between groups. For the vertebroplasty group, polymethylmethacrylate bone cement was injected into the fractured vertebral body under fluoroscopy. Cyclic compression (685-1370 N sinusoid) was performed on all spine segments for 115,000 cycles. Micro-CT scans were obtained before and after cyclic loading to quantify endplate subsidence. Maximum subsidence was compared between groups in the caudal endplate of the superior adjacent vertebra (SVcau); cranial (TVcra) and caudal (TVcau) endplates of the treated vertebra; and the cranial endplate of the inferior adjacent vertebra (IVcra). In addition, micro-CT images were used to quantify average endplate thickness and trabecular bone volume fraction. These parameters were then correlated with maximum endplate subsidence for each endplate. RESULTS: The maximum subsidence in SVcau endplate for the vertebroplasty group (0.34 ± 0.58 mm) was significantly (p < 0.05) greater than for the control group (-0.13 ± 0.27 mm). Maximum subsidence in the TVcra, TVcau, and IVcra endplates were greater in the vertebroplasty group, but these differences were not significant (p > 0.16). Increased subsidence in the vertebroplasty group manifested locally in the anterior region of the SVcau endplate and in the posterior region of the TVcra and TVcau endplates (p < 0.10). Increased subsidence was observed in thinner endplates with lower trabecular bone volume fraction for both vertebroplasty and control groups (R(2) correlation up to 62%). In the SVcau endplate specifically, these 2 covariates aided in understanding subsidence differences between vertebroplasty and control groups. CONCLUSIONS: Bone cement injected during vertebroplasty alters local biomechanics in elderly female spines, resulting in increased endplate disruption in treated and superior adjacent vertebrae. More specifically, bone cement increases subsidence in the posterior regions of the treated endplates and the anterior region of the superior caudal endplate. This increased subsidence may be the initial mechanism leading to subsequent compression fractures after vertebroplasty, particularly in vertebrae superior to the treated level.

Nerve growth factor promotes expression of novel genes in intervertebral disc cells that regulate tissue degradation: Laboratory investigation.

OBJECT: Increased neurotrophin activity in degenerative intervertebral discs (IVDs) is one potential cause of chronic low-back pain (LBP). The aim of the study was to assess if nerve growth factor (NGF) might alter gene expression of IVD cells and contribute to disc degeneration by enhancing expression or activity of factors that cause breakdown of IVD matrix. METHODS: Rat-tail IVD cells were stimulated by NGF and subjected to microarray analysis. Real-time polymerase chain reaction, Western blotting, and immunocytochemistry of rat and human IVD cells and tissues treated with NGF in vitro in the absence or presence of the NGF inhibitor Ro 08-2750 were used to confirm findings of the microarray studies. Phosphorylation of mitogen-activated protein kinase (MAPK) was used to identify cell signaling pathways involved in NGF stimulation in the absence or presence of Ro 08-2750. RESULTS: Microarray analysis demonstrated increased expression of chitinase 3-like 1 (Chi3l1), lipocalin 2 (Lcn2), and matrix metalloproteinase-3 (Mmp3) following NGF stimulation of rat IVD cells in vitro. Increased gene expression was confirmed by real-time polymerase chain reaction with a relative increase in the Mmp/Timp ratio. Increased expression of Chi3l1, Lcn2, and Mmp3 following NGF stimulation was also demonstrated in rat cells and human tissue in vitro. Effects of NGF on protein expression were blocked by an NGF inhibitor and appear to function through the extracellular-regulation kinase 1/2 (ERK1/2) MAPK pathway. CONCLUSIONS: Nerve growth factor has potential effects on matrix turnover activity and influences the catabolic/anabolic balance of IVD cells in an adverse way that may potentiate IVD degeneration. Anti-NGF treatment might be beneficial to ameliorate progressive tissue breakdown in IVD degeneration and may lead to pain relief.