Fatty infiltration in cervical flexors and extensors in patients with degenerative cervical myelopathy using a multi-muscle segmentation model.

BACKGROUND: In patients with degenerative cervical myelopathy (DCM) that have spinal cord compression and sensorimotor deficits, surgical decompression is often performed. However, there is heterogeneity in clinical presentation and post-surgical functional recovery. OBJECTIVES: Primary: a) to assess differences in muscle fat infiltration (MFI) in patients with DCM versus controls, b) to assess association between MFI and clinical disability. Secondary: to assess association between MFI pre-surgery and post-surgical functional recovery. STUDY DESIGN: Cross-sectional case control study. METHODS: Eighteen patients with DCM (58.6 ± 14.2 years, 10 M/8F) and 25 controls (52.6 ± 11.8 years, 13M/12 F) underwent 3D Dixon fat-water imaging. A convolutional neural network (CNN) was used to segment cervical muscles (MFSS- multifidus and semispinalis cervicis, LC- longus capitis/colli) and quantify MFI. Modified Japanese Orthopedic Association (mJOA) and Nurick were collected. RESULTS: Patients with DCM had significantly higher MFI in MFSS (20.63 ± 5.43 vs 17.04 ± 5.24, p = 0.043) and LC (18.74 ± 6.7 vs 13.66 ± 4.91, p = 0.021) than controls. Patients with increased MFI in LC and MFSS had higher disability (LC: Nurick (Spearman's ρ = 0.436, p = 0.003) and mJOA (ρ = -0.399, p = 0.008)). Increased MFI in LC pre-surgery was associated with post-surgical improvement in Nurick (ρ = -0.664, p = 0.026) and mJOA (ρ = -0.603, p = 0.049). CONCLUSION: In DCM, increased muscle adiposity is significantly associated with sensorimotor deficits, clinical disability, and functional recovery after surgery. Accurate and time efficient evaluation of fat infiltration in cervical muscles may be conducted through implementation of CNN models.

Zonisamide ameliorates progression of cervical spondylotic myelopathy in a rat model.

Cervical spondylotic myelopathy (CSM) is caused by chronic compression of the spinal cord and is the most common cause of myelopathy in adults. No drug is currently available to mitigate CSM. Herein, we made a rat model of CSM by epidurally implanting an expanding water-absorbent polymer underneath the laminae compress the spinal cord. The CSM rats exhibited progressive motor impairments recapitulating human CSM. CSM rats had loss of spinal motor neurons, and increased lipid peroxidation in the spinal cord. Zonisamide (ZNS) is clinically used for epilepsy and Parkinson's disease. We previously reported that ZNS protected primary spinal motor neurons against oxidative stress. We thus examined the effects of ZNS on our rat CSM model. CSM rats with daily intragastric administration of 0.5% methylcellulose (n = 11) and ZNS (30 mg/kg/day) in 0.5% methylcellulose (n = 11). Oral administration of ZNS ameliorated the progression of motor impairments, spared the number of spinal motor neurons, and preserved myelination of the pyramidal tracts. In addition, ZNS increased gene expressions of cystine/glutamate exchange transporter (xCT) and metallothionein 2A in the spinal cord in CSM rats, and also in the primary astrocytes. ZNS increased the glutathione (GSH) level in the spinal motor neurons of CSM rats. ZNS potentially ameliorates loss of the spinal motor neurons and demyelination of the pyramidal tracts in patients with CSM.

TNF-α induces apoptosis of human nucleus pulposus cells via activating the TRIM14/NF-κB signalling pathway.

Cervical spondylosis is a degenerative disease commonly found in older adults and characterized by progressive osteophyte formation and disc collapse. Apoptosis in nucleus pulposus (NP) cells which induced by TNF-α has been widely known to associate with the disc degeneration. However, the exactly underlying molecular mechanism was still unclear. The aim of our study was to investigate whether TRIM14/NF-κB signalling pathway is associated with the apoptosis of human NP cells (HNPC) induced by TNF-α. Our data demonstrated that TNF-α treatment obviously decreased the cell viability, induced apoptosis and increased TRIM14 expression and NF-κBp65 activity in HNPC in a dose-dependent manner. Down-regulation of TRIM14 or NF-κB inhibitor PDTC treatment significantly inhibited cell apoptosis, Bax/Bcl-2 ratio and NF-κBp65 activation induced by TNF-α in HNPC. Meanwhile, up-regulation of TRIM14 obviously increased cell apoptosis, Bax/Bcl-2 ratio and NF-κBp65 activation in HNPC. Then, we found that the protein PPM1A was identified as a binding partner of TRIM14 and ubiquitinated by TRIM14. These findings provide insights into the function of TRIM14 and NF-κB signalling and might, therefore, represent a novel therapeutic target for treatment of cervical spondylosis.

Cervical spondylotic myelopathy: Changes of fractional anisotropy in the spinal cord and magnetic resonance spectroscopy of the primary motor cortex in relation to clinical symptoms and their duration.

OBJECTIVE: To determine the changes in fractional anisotropy (FA) at the proximal spinal cord and in magnetic resonance spectroscopy (MRS) of the precentral gyrus in patients with cervical spondylotic myelopathy (CSM) with respect to clinical symptoms and their duration. MATERIAL AND METHODS: 20 patients with CSM (7 female; mean age 64.6 ± 10.5 years) and 18 age/sex matched healthy controls (9 female; mean age 63.5 ± 6.6 years) were prospectively included. Clinical data (modified Japanese Orthopaedic Association Score (mJOA) and Neck Disability Index (NDI)) and 3T MR measurements including DTI at the spinal cord (level C2/3) with FA and MRS of the left and right precentral gyrus were taken. Clinical correlations and regression analyses were performed. RESULTS: Mean clinical scores of patients were significantly different to controls (mJOA; CSM: 10.2 ± 2.9; controls: 18.0 ± 0.0, p < 0.001; NDI; CSM: 41.4±23.5; controls: 4.4±6.6, p<0.001); FA was significantly lower in patients (CSM: 0.645 ± 0.067; controls: 0.699 ± 0.037, p = 0.005). MRS showed significantly lower metabolite concentrations between both groups: creatine (Cr) (CSM: 46.46±7.64; controls: 51.36±5.76, p = 0.03) and N-acetylaspartate (NAA) (CSM: 93.94±19.22; controls: 107.24±20.20, p = 0.05). Duration of symptoms ≤6 months was associated with increased myo-inositol (Ins) (61.58±17.76; 44.44±10.79; p = 0.02) and Ins/Cr ratio (1.36±0.47; 0.96±0.18; p = 0.014) compared to symptoms >6 months. CONCLUSION: Metabolic profiles of the precentral gyrus and FA in the uppermost spinal cord differ significantly between patients and healthy controls. Ins, thought to be a marker of endogenous neuroinflammatory response, is high in the early course of CSM and normalizes over time.

Expression profile of long non-coding RNAs in cervical spondylotic myelopathy of rats by microarray and bioinformatics analysis.

INTRODUCTION: It has been reported that a wide range of long non-coding RNAs (lncRNAs) are implicated in numerous diseases such as tumor, cardiopathy and neurological disorders. Identifying the differentially expressed (DE) profile of lncRNAs in cervical spondylotic myelopathy (CSM) is essential to understand the mechanisms of CSM. METHODS: Microarray assay, quantitative real-time PCR (qRT-PCR) and bioinformatics analysis were employed to reveal the DE profile and potential functions of lncRNAs in CSM. RESULTS: Microarray analysis displayed the DE profiles of lncRNAs and mRNAs in rats between the CSM group and the control (CON) group. Thereinto, 1266 DE lncRNAs (738 up-regulation and 528 down-regulation) and 847 mRNAs (487 up-regulation and 360 down-regulation) with >1.1 fold change (FC) were finally identified. Moreover, 17 lncRNAs (13 up-regulation and 4 down-regulation) and 18 mRNAs (13 up-regulation and 5 down-regulation) were found deregulated by >2 FC. Further bioinformatics analysis showed the most remarkable biological processes among up-regulated RNAs contain cellular response to interferon-beta, inflammatory response and innate immune response, which may involve in CSM. Besides, related DE mRNAs of 17 DE lncRNAs in the genome were related to signaling pathway about NOD-like receptor, TNF, and apoptosis. In addition, a co-expression network of lncRNA-mRNA was established for analyzing the biological roles of lncRNAs. Among these, we found a ceRNA network related to CSM. Finally, the expressions of the DE lncRNAs and ceRNA network confirmed by qRT-PCR were in agreement with microarray data. CONCLUSIONS: Our study revealed the DE profiles of lncRNAs and mRNAs for CSM. Those dysregulated RNAs may represent potential therapeutic targets of CSM for further study.

Exploration about changes of IL-10, NF-κB and MMP-3 in a rat model of cervical spondylosis.

OBJECTIVES: To investigate the relationship and mechanism between IL-10, NF-κB and MMP-3 in cervical degenerative disease induced by unbalanced dynamic and static forces in rats. METHODS: Sixty Sprague Dawley rats were randomized into test (n=45) and control (n=15) groups, which were randomly subdivided into three groups corresponding to one-month, three-month and six-month post-operation. Test group included 10, 15, 20 rats at corresponding postoperative stage and control group had five rats at each time point. By excising cervicodorsal muscles and ligaments of rats to establish unbalanced dynamic and static rat model in test group. The expression of IL-10, NF-κB and MMP-3 in the intervertebral disc tissue samples of both test and control group rats were detected by immunohistochemistry at one-month, three-month and six-month post-operation. The results were analyzed and compared among groups. RESULTS: Compared with the control group, the positive expression of IL-10 in test group was significantly higher at three-month (P<0.05). In the same model group, IL-10 was highest at one-month. Compared with the control group, NF-kB in test group was higher at one-month, three-month and six-month. In the same model group, NF-kB was the highest at one-month, followed by the time at three-month and six-month. And, compared with the control group, MMP-3 was significantly higher in test group at one-month (P<0.05). CONCLUSION: Cervical degeneration may accompanied with the changes of IL-10, NF-κB and MMP-3.

Metabolic Imaging Using Proton Magnetic Spectroscopy as a Predictor of Outcome After Surgery for Cervical Spondylotic Myelopathy.

STUDY DESIGN: A single-center magnetic resonance spectroscopy (MRS) imaging and surgical outcome study involving 16 patients with cervical spondylotic myelopathy (CSM). OBJECTIVE: In the present study, we assess the utility of MRS to quantify metabolic changes within the spinal cord and predict surgical outcome in CSM patients. SUMMARY OF BACKGROUND DATA: MRS is an advanced spinal imaging modality that can provide pertinent metabolic and biochemical information regarding spinal cord function. Previous studies have demonstrated significant abnormalities in specific cellular metabolite concentrations in CSM patients. METHODS: Sixteen patients with CSM were evaluated. Single voxel MRS was performed in the cervical cord. N-acetyl-aspartate (NAA) and choline metabolite concentration ratios with respect to creatine were quantified, as well as the presence or absence of a lactate peak. The modified Japanese Orthopaedic Association (mJOA) scale was used as the functional assessment measure. Correlation of MRS metabolites with change in mJOA score was performed. RESULTS: The mean follow-up time was 19 months. There was a statistically significant improvement between mean preoperative and postoperative mJOA score after surgery (P<0.0001). The NAA/Cr ratio demonstrated a significant relationship to the change in mJOA score after surgery (P=0.0479; R=0.2513). The Cho/NAA ratio demonstrated an even stronger correlation with the change in mJOA score after surgery (P=0.0065; R=0.4219). Neither the Cho/Cr ratio, nor the presence of a lactate peak or T2-weighted signal change was significantly correlated with change in mJOA score after surgery. CONCLUSIONS: MRS is a novel, noninvasive imaging modality that provides pertinent information regarding spinal cord cellular and metabolic function. In a cohort of operatively treated CSM patients, the NAA/Cr and Cho/NAA ratios were predictive of neurological outcome, as both were significantly associated with change in mJOA score after surgery.

Remote motor system metabolic profile and surgery outcome in cervical spondylotic myelopathy.

OBJECTIVE In patients with cervical spondylotic myelopathy (CSM), the motor system may undergo progressive functional/structural changes rostral to the lesion, and these changes may be associated with clinical disability. The extent to which these changes have a prognostic value in the clinical recovery after surgical treatment is not yet known. In this study, magnetic resonance spectroscopy (MRS) was used to test 2 primary hypotheses. 1) Based on evidence of corticospinal and spinocerebellar, rubro-, or reticulospinal tract degeneration/dysfunction during chronic spinal cord compression, the authors hypothesized that the metabolic profile of the primary motor cortices (M1s) and cerebellum, respectively, would be altered in patients with CSM, and these alterations would be associated with the extent of the neurological disabilities. 2) Considering that damage and/or plasticity in the remote motor system may contribute to clinical recovery, they hypothesized that M1 and cerebellar metabolic profiles would predict, at least in part, surgical outcome. METHODS The metabolic profile, consisting of N-acetylaspartate (NAA; marker of neuronal integrity), myoinositol (glial marker), choline (cell membrane synthesis and turnover), and glutamate-glutamine (glutamatergic system), of the M1 hand/arm territory in each hemisphere and the cerebellum vermis was investigated prior to surgery in 21 patients exhibiting weakness of the upper extremities and/or gait abnormalities. Age- and sex-matched controls (n = 16) were also evaluated to estimate the pre-CSM metabolic profile of these areas. Correlation and regression analyses were performed between preoperative metabolite levels and clinical status 6 months after surgery. RESULTS Relative to controls, patients exhibited significantly higher levels of choline but no difference in the levels of other metabolites across M1s. Cerebellar metabolite levels were indistinguishable from control levels. Certain metabolites-myo-inositol and choline across M1s, NAA and glutamate-glutamine in the left M1, and myo-inositol and glutamate-glutamine in the cerebellum-were significantly associated with postoperative clinical status. These associations were greatly improved by including preoperative clinical metrics into the models. Likewise, these models improved the predictive value of preoperative clinical metrics alone. CONCLUSIONS These preliminary findings demonstrate relationships between the preoperative metabolic profiles of two remote motor areas and surgical outcome in CSM patients. Including preoperative clinical metrics in the models significantly strengthened the predictive value. Although further studies are needed, this investigation provides an important starting point to understand how the changes upstream from the injury may influence the effect of spinal cord decompression.

Metabolite and functional profile of patients with cervical spondylotic myelopathy.

OBJECTIVE The goal of this study was to compare the recovery of neuronal metabolism and functional reorganization in the primary motor cortex (M1) between mild and moderate cervical spondylotic myelopathy (CSM) following surgical intervention. METHODS Twenty-eight patients with CSM underwent 3-T MRI scans that included spectroscopy and functional MRI, before surgery and 6 months postsurgery. The classification of severity was based on the modified Japanese Orthopaedic Association questionnaire. Mild and moderate myelopathy were defined by modified Japanese Orthopaedic Association scores > 12 of 18 (n = 15) and 9-12 (n = 13), respectively. Ten healthy control subjects underwent 2 MRI scans 6 months apart. Metabolite levels were measured in the M1 contralateral to the greater deficit side in patients with CSM and on both sides in the controls. Motor function was assessed using a right finger-tapping paradigm and analyzed with BrainVoyager QX. RESULTS Patients with mild CSM had a lower preoperative N-acetylaspartate to creatine (NAA/Cr) ratio compared with moderate CSM, suggesting mitochondrial dysfunction. Postsurgery, NAA/Cr in moderate CSM decreased to the levels observed in mild CSM. Preoperatively, patients with mild CSM had a larger volume of activation (VOA) in the M1 than those with moderate CSM. Postoperatively, the VOAs were comparable between the mild and moderate CSM groups and had shifted toward the primary sensory cortex. CONCLUSIONS The NAA/Cr ratio and VOA size in the M1 can be used to discriminate between mild and moderate CSM. Postsurgery, the metabolite profile of the M1 did not recover in either group, despite significant clinical improvement. The authors proposed that metabolic impairment in the M1 may trigger the recruitment of adjacent healthy cortex to achieve functional recovery.

Cervical Spondylotic Myelopathy: Metabolite Changes in the Primary Motor Cortex after Surgery.

Purpose To characterize longitudinal metabolite alterations in the motor cortex of patients with cervical spondylotic myelopathy (CSM) by using proton magnetic resonance (MR) spectroscopy and to evaluate white matter integrity with diffusion-tensor imaging in patients who are recovering neurologic function after decompression surgery. Materials and Methods Informed written consent was obtained for all procedures and the study was approved by Western University's Health Sciences Research Ethics Board. Twenty-eight patients with CSM and 10 healthy control subjects were prospectively recruited and underwent two separate 3-T MR imaging examinations 6 months apart. Patients with CSM underwent surgery after the first examination. N-acetylaspartate (NAA), an indicator of neuronal mitochondrial function, normalized to creatine (Cr) levels were measured from the motor cortex contralateral to the greater functional deficit side in the patient group and on both sides in the control group. Fractional anisotropy and mean diffusivity were measured by means of diffusion-tensor imaging in the white matter adjacent to the motor and sensory cortices of the hand and the entire cerebral white matter. Clinical data were analyzed by using Student t tests. Results In patients with CSM, NAA normalized to Cr (NAA/Cr) levels were significantly lower 6 months after surgery (1.48 ± 0.08; P < .03) compared with preoperative levels (1.73 ± 0.09), despite significant improvement in clinical questionnaire scores. Fractional anisotropy and mean diffusivity were the same (P > .05) between the patient and control groups in all measured regions at all time points. Conclusion NAA/Cr levels decreased in the motor cortex in patients with CSM 6 months after successful surgery. Intact white matter integrity with decreased NAA/Cr levels suggests that mitochondrial metabolic dysfunction persists after surgery. © RSNA, 2016 Online supplemental material is available for this article.

Mechanoreceptors in Diseased Cervical Intervertebral Disc and Vertigo.

STUDY DESIGN: We collected the samples of cervical intervertebral discs from patients with vertigo to examine the distribution and types of mechanoreceptors in diseased cervical disc. OBJECTIVE: The aim of this study was to determine whether mechanoreceptors are distributed more abundantly in cervical discs from patients with cervical spondylosis, and whether they are related to vertigo. SUMMARY OF BACKGROUND DATA: Previous limited studies have found that normal cervical intervertebral discs are supplied with mechanoreceptors that have been considered responsible for proprioceptive functions. Several clinical studies have indicated that the patients with cervical spondylosis manifested significantly impaired postural control and subjective balance disturbance. METHODS: We collected 77 samples of cervical discs from 62 cervical spondylosis patients without vertigo, 61 samples from 54 patients with vertigo, and 40 control samples from 8 cadaveric donors to investigate distribution of mechanoreceptors containing neurofilament (NF200) and S-100 protein immunoreactive nerve endings. RESULTS: The immunohistochemical investigation revealed that the most frequently encountered mechanoreceptors were the Ruffini corpuscles in all groups of cervical disc samples. They were obviously increased in the number and deeply ingrown into inner annulus fibrosus and even into nucleus pulposus in the diseased cervical discs from patients with vertigo in comparison with the discs from patients without vertigo and control discs. Only three Golgi endings were seen in the three samples from patients with vertigo. No Pacinian corpuscles were found in any samples of cervical discs. CONCLUSION: The diseased cervical discs from patients with vertigo had more abundant distribution of Ruffini corpuscles than other discs. A positive association between the increased number and ingrowth of Ruffini corpuscles in the diseased cervical disc and the incidence of vertigo in the patients with cervical spondylosis was found, which may indicate a key role of Ruffini corpuscles in the pathogenesis of vertigo of cervical origin. LEVEL OF EVIDENCE: 1.

N-acetylaspartate in the motor and sensory cortices following functional recovery after surgery for cervical spondylotic myelopathy.

OBJECTIVE Cervical spondylotic myelopathy (CSM) is the most common cause of reversible spinal cord dysfunction in people over the age of 55 years. Following surgery for symptomatic CSM, patients demonstrate motor improvement early in the postoperative course, whereas sensory improvement can lag behind. The authors of the present study hypothesized that changes in the concentration of N-acetylaspartate (NAA) in the motor and sensory cortices in the brain would emulate the time course of neurological recovery following decompression surgery for CSM. Their aim was to compare and contrast how metabolite levels in the motor and sensory cortices change after surgery to reverse downstream spinal cord compression. METHODS Twenty-four patients with CSM and 8 control subjects were studied using proton MR spectroscopy (1H-MRS) images acquired on a 3.0-T Siemens MRI unit. The 1H-MRS data (TE 135 msec, TR 2000 msec) were acquired to measure absolute levels of NAA from the motor and sensory cortices in the cerebral hemisphere contralateral to the side of greater deficit at baseline in each subject. Data were also acquired at 6 weeks and 6 months following surgery. Control subjects were also evaluated at 6 weeks and 6 months following baseline data acquisition. Neurological function was measured in each subject at all time points using the Neck Disability Index (NDI), modified Japanese Orthopaedic Association (mJOA) questionnaire, and the American Spinal Injury Association (ASIA) neurological classification. RESULTS In the motor cortex of patients, NAA levels decreased significantly (p < 0.05) at 6 weeks and 6 months postsurgery compared with baseline levels. In the sensory cortex of patients, NAA levels decreased significantly (p < 0.05) only at 6 months after surgery compared with baseline and 6-week levels. No significant changes in NAA were found in control subjects. Clinical scores demonstrated significant (p < 0.05) motor recovery by 6 weeks, whereas sensory improvements (p < 0.05) appeared at only 6 months. CONCLUSIONS Findings suggest that metabolite changes in both the motor and sensory cortices mimic the time course of functional motor and sensory recovery in patients with CSM. The temporal course of neurological recovery may be influenced by metabolic changes in respective cortical regions.

[Effect of acupotomy intervention on cervicomuscular apoptosis in cervical spondylosis rabbits].

OBJECTIVE: To observe the effect of acupotomy therapy on cervicomuscular apoptosis and apoptosis regulator Bax protein expression in cervical spondylosis (CS) rabbits so as to investigate its mechanisms underlying improvement of CS. METHODS: Twenty-four New Zealand rabbits were randomly divided into normal control, model, acupotomy and electroacupuncture (EA) groups, with 6 rabbits in each group. The CS model was made by forced head-bowing for 5 hours in a restrained chamber, once daily for 12 weeks. Acupotomy was performed at the starting point of trapezius, the mastoid process attaching point of sternocleidomastoid, the cerverical vertebrae joint process or the local induration or cord-like mass (2 or 3 points of them were used as the needle-knife entering points), once a week for 3 weeks. For animals of the EA group, EA (2 Hz/100 Hz, 2 mA) was applied to bilateral "Tianzhu" (BL 10), "Jingbailao" (EX-HN 15), "Dazhu" (BL 11) for 20 min, once daily and 3 times a week for 3 weeks. The number of apoptotic cells in the cervical muscle was observed by light microscope after TUNEL staining and muscular Bcl-2 and Bax protein expression was detected by Western blot. RESULTS: In comparison with the control group, the number of cervicomuscular apoptotic cells, and the expression level of cervicomuscular Bax protein were significantly increased, and the Bcl-2/Bax was obviously decreased in the model group (P < 0.01, P < 0.05). Compared to the model group, the number of apoptotic cells and the expression level of muscular Bax protein were notably decreased in the acupotomy group (P < 0.01, P < 0.05), while the ratio of Bcl-2 and Bax was apparently increased in the acupotomy group (P < 0.05). The effects of acupotomy were significantly superior to those of EA in lowering apoptotic cell number and in up-regulating Bcl-2/Bax (P < 0.01, P < 0.05). No significant differences were found between the EA and model groups in the apoptotic cell number and among the four groups in Bcl-2 protein expression levels (P > 0.05). CONCLUSION: Acupotomy therapy can reduce cervicomuscular cellular apoptosis and Bax protein expression in CS rabbits, which may be one of its mechanism underlying improving CS.

Electroacupuncture inhibits annulus fibrosis cell apoptosis in vivo via TNF-α-TNFR1-caspase-8 and integrin ß1/Akt signaling pathways.

OBJECTIVE: To examine whether electroacupuncture (EA) treatment inhibited cell apoptosis of intervertebral annulus fibrosis (AF) via tumor necrosis factor-α (TNF-α)-tumor necrosis factor receptor 1 (TNFR1)-caspase-8 and integrin ß1/Akt signaling pathways in a rat model of cervical intervertebral disc degeneration caused by unbalanced dynamic and static forces. METHODS: Thirty-two Sprague-Dawley rats were included in this study, of which 24 rats underwent surgery to induce cervical intervertebral disc degeneration, while eight rats received EA treatment at Dazhui (GV 14). Immunohistochemical staining was used to detect TNF-α, TNFR1, and caspase-8. Apoptosis of AF cells was examined with terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining. The mRNA and protein expression levels of integrin ß1 and Akt were evaluated with real-time polymerase chain reaction and western blot analysis, respectively. RESULTS: Treatment with EA decreased TUNEL-positive AF cells and lowered TNF-α, TNFR1 and caspase-8 positive cells compared with control groups. EA treatment also increased integrin ß1 and Akt mRNA and protein levels compared with controls. CONCLUSION: Treatment with EA inhibits AF cell apoptosis through suppression of the TNF-α-TNFR1-caspase-8 signal pathway and increases the expression of integrin ß1 and Akt. EA may be a good alternative therapy for treating cervical spondylosis.

[Effects of electroacupuncture on Wnt-ß-catenin signal pathway in annulus fibrosus cells in intervertebral disc in rats with cervical spondylosis].

OBJECTIVE: To observe the effects of electroacupuncture (EA) at "Dazhui" (GV 14) on Wnt-ß-catenin signal pathway in annulus fibrosus cells in intervertebral disc in rats with cervical spondylosis. METHODS: Forty SD rats were randomized into a control group, a model group, an EA group and a medication group, 10 rats in each one. Rats in the control group were treated with sham operation, only incision on local skin; rats in the remaining groups were made into cervical spondylosis models. After model establishment, rats in the control group and model group received fixed treatment under identical condition; rats in the EA group were treated with EA at "Dazhui" (GV 14), 30 min per treatment; rats in the medication group were treated with intragastric administration of meloxicam tablets. Treatments were both given once a day, and 14 days were taken as one session; there was an interval of 2 days between two sessions, and totally two sessions were given. After the treatments, immunohistochemistry was applied to measure the expression of Wnt, glycogen synthase kinase-3ß (GSK-3ß) and Axin in annulus fibrosus cells; western blot was used to test the expression of P-ß-catenin. RESULTS: In the control group, there were more positive cells of Wnt, GSK-3ß and Axin, which were intensively distributed, deeply colored, and strongly positive; In the model group, there were less positive cells of Wnt, GSK-3ß and Axin, which were sparsely distributed and weakly positive. The expression of Wnt, GSK-3ß, Axin and P-ß-catenin in the model group was less than that in the control group (all P < 0.05); expression of Wnt, GSK-3ß, Axin and P-ß-catenin in the EA group and medication group was higher than that in the model group (all P < 0.05); expression of Wnt, GSK-3ß, Axin and P-ß-catenin was not significantly different between EA group and medication group (all P > 0.05). CONCLUSION: EA could delay the degeneration of intervertebral disc, which may be related to EA inhibiting signal pathway of Wnt-ß-catenin.

Clinical value of 2-deoxy-[18F]fluoro-D-glucose positron emission tomography in patients with cervical spondylotic myelopathy.

Cervical spondylotic myelopathy (CSM) is one of the most common spinal cord disorders in the elderly. It is usually diagnosed by MRI, but in a significant number of patients the clinical course of CSM does not correlate with the extent of the spinal cord compression. Recent studies have suggested that a distinct metabolic pattern of the cervical cord, as assessed by PET with 2-deoxy-[(18)F]fluoro-D-glucose ((18)F-FDG) may predict a patient's clinical outcome after decompressive surgery for cervical spine stenosis. The authors provide an overview of the recent literature regarding the value of PET with (18)F-FDG of the cervical cord in patients with CSM, paying attention to prognostic aspects and the potential role of inflammatory processes in the acute phase of the disease.

Proton magnetic resonance spectroscopy of human cervical spondylosis at 3T.

STUDY DESIGN: A single-center magnetic resonance imaging and spectroscopic study involving 21 patients with advanced cervical spondylosis and 11 healthy controls. OBJECTIVE: We assessed the utility of magnetic resonance spectroscopy (MRS) to quantify biochemical changes within the spinal cord and serve as a potential biomarker in patients with cervical spondylosis with or without T2 hyperintensity within the cord. SETTING: Los Angeles, California, USA. METHODS: Twenty-one patients with cervical spondylosis and eleven healthy controls were evaluated. Single-voxel MRS was performed in the cervical cord. Morphometry of the spinal canal space was measured. N-Acetyl aspartylglutamic acid (NAA), choline (Cho), myo-inositol (Myo-I), glutamine-glutamate complex (Glx) and lactate metabolite concentration ratios with respect to total creatine (Cr) were quantified using an LC model algorithm and compared between healthy controls and spondylosis patients. Correlation of MRS metabolites with modified Japanese Orthopaedic Association (mJOA) score was also performed. RESULTS: The spinal canal space was significantly different between patients and controls (analysis of variance (ANOVA), P<0.0001). Total Cho-to-Cr ratio was significantly elevated in patients with spondylosis and T2-hyperintensity compared with healthy controls (ANOVA, P<0.01). A significantly higher Cho-to-NAA ratio was observed in spondylosis patients compared with healthy controls (ANOVA, P<0.01). Slightly elevated Glx and Myo-I were encountered in patients with stenosis without T2 hyperintensity. A linear correlation between Cho-NAA ratio and mJOA was also observed (P<0.01). CONCLUSION: MRS appears sensitive to biochemical changes occurring in advanced cervical spondylosis patients. The Cho/NAA ratio was significantly correlated with the mJOA score, providing a potentially clinically useful radiographical biomarker for the management of advanced cervical spondylosis patients.

Immunohistochemical profile of NF-κB/p50, NF-κB/p65, MMP-9, MMP-2, and u-PA in experimental cervical spondylotic myelopathy.

STUDY DESIGN: The immunohistochemical profile of nuclear factor-κ B (NF-κB)/p50, NF-κB/p65, matrix metalloproteinase (MMP)-9, MMP-2, and urokinase-type plasminogen activator (u-PA) proteins was examined in spinal cord tissues coming from rabbits, which underwent chronic cervical spinal cord compression. OBJECTIVE: To study the potential role of NF-κB and extracellular matrix proteins under the chronic mechanical compression of the cervical spinal cord. SUMMARY OF BACKGROUND DATA: Cervical spondylotic myelopathy (CSM) is the most common cause of spinal cord dysfunction among adults older than 55 years. Neuronal loss, myelin destruction, axonal degeneration, and glial scar formation are the principal neuropathological features of CSM. However, the biologic pathways that lead to these features remain unclear. METHODS: In this study, we used a new animal experimental model of CSM developed in our laboratory. Briefly, after posterior cervical laminectomy, gradual and progressive compression (during 20 weeks) was achieved by introducing a piece of aromatic polyether (0.07 mm thick) under the C6 lamina in 15 New Zealand rabbits. In control animals (n = 15), the aromatic polyether was implanted and then removed after 60 seconds (sham operation). The immunoreactivity of p50 and p65 subunits of NF-kB, as well as that of MMP-2, MMP-9, and u-PA, was evaluated in paraffin-embedded spinal cord sections coming from both groups. The evaluation was performed using immunohistochemistry technique and the results were analyzed using SPSS for Windows, release 12.0 (SPSS Inc., Chicago, IL). RESULTS: Increased immunoreactivity of both NF-κB subunits, p50 and p65, as well as MMP-2, MMP-9, and u-PA was demonstrated in animals with CSM in comparison with controls. Statistical analysis of the results revealed strong positive correlation between NF-κB subunits immunoreactivity and that of MMP-9, MMP-2, and u-PA. CONCLUSION: There is a strong correlation between the immunoexpression of NF-κB/p50, NF-κB/p65, MMP-2, MMP-9, u-PA, and CSM.

Spinal multifocal amyloidosis derived from wild-type transthyretin.

Abstract Spinal amyloidosis can occur as a part of systemic amyloidosis or as localized amyloidomas. However, the exact pathogenesis of the spinal amyloidosis remains to be fully understood. Transthyretin (TTR) is an amyloidogenic protein causing two kinds of amyloid diseases. One is senile systemic amyloidosis (SSA), which is caused by wild-type (WT) TTR and primarily affects cardiac functions. The other type is familial amyloidosis, which is mainly induced by mutated TTR. We report here the first case of multifocal spinal TTR amyloidosis derived from WT TTR with radiculomyelopathy and destructive spondylosis. The data and clinical manifestations suggest that the patient may develop SSA. Clinical manifestations of TTR-related amyloidosis may vary more than we previously thought. In spinal amyloidosis, WT TTR is one of the candidate precursor proteins for the disease.

Proton magnetic resonance spectroscopy to evaluate spinal cord axonal injury in cervical spondylotic myelopathy.

OBJECT: Magnetic resonance spectroscopy is commonly used to provide cellular and metabolic information in the management of a variety of pathological processes that affect the brain, and its application recently has been expanded to the cervical spine. The majority of radiographic investigations into the pathophysiology of cervical spondylotic myelopathy (CSM) have been focused on the spinal cord macrostructure. The authors sought to determine the feasibility of using MR spectroscopy to analyze spinal cord biochemical function in patients with CSM. METHODS: Twenty-one patients with clinical and radiographic evidence of CSM were prospectively enrolled in this study. The patients underwent preoperative neurological examination, functional assessment, and cervical spine MR spectroscopy. Voxels were placed at the C-2 level, and the MR spectroscopy spectra peaks for N-acetylaspartate (NAA), choline, lactate (Lac), and creatine (Cr) were measured. Thirteen age-matched healthy volunteers served as controls. RESULTS: The NAA/Cr ratio was significantly lower in patients with CSM than in controls (1.27 vs 1.83, respectively, p < 0.0001). The choline/Cr ratio was not significantly different between the 2 groups. Seven of the patients with CSM had a Lac peak, whereas no peaks were noted in the control group (p < 0.05). There was no correlation between the severity of myelopathy and the NAA/Cr ratio in the CSM cohort. CONCLUSIONS: Data in this study demonstrated the feasibility of using MR spectroscopy to evaluate the cellular biochemistry of the spinal cord in patients with CSM. Patients with CSM had a significantly lower NAA/Cr ratio than healthy controls, likely because of axonal and neuronal loss. The presence of Lac peaks in one-third of the patients in the CSM cohort further supports the role of ischemia in the pathophysiology of CSM.