Human neuropathological and animal model evidence supporting a role for Fas-mediated apoptosis and inflammation in cervical spondylotic myelopathy.

Although cervical spondylotic myelopathy is a common cause of chronic spinal cord dysfunction in humans, little is known about the molecular mechanisms underlying the progressive neural degeneration characterized by this condition. Based on animal models of cervical spondylotic myelopathy and traumatic spinal cord injury, we hypothesized that Fas-mediated apoptosis and inflammation may play an important role in the pathobiology of human cervical spondylotic myelopathy. We further hypothesized that neutralization of the Fas ligand using a function-blocking antibody would reduce cell death, attenuate inflammation, promote axonal repair and enhance functional neurological outcomes in animal models of cervical spondylotic myelopathy. We examined molecular changes in post-mortem human spinal cord tissue from eight patients with cervical spondylotic myelopathy and four control cases. Complementary studies were conducted using a mouse model of cervical spondylotic myelopathy (twy/twy mice that develop spontaneous cord compression at C2-C3). We observed Fas-mediated apoptosis of neurons and oligodendrocytes and an increase in inflammatory cells in the compressed spinal cords of patients with cervical spondylotic myelopathy. Furthermore, neutralization of Fas ligand with a function-blocking antibody in twy/twy mice reduced neural inflammation at the lesion mediated by macrophages and activated microglia, glial scar formation and caspase-9 activation. It was also associated with increased expression of Bcl-2 and promoted dramatic functional neurological recovery. Our data demonstrate, for the first time in humans, the potential contribution of Fas-mediated cell death and inflammation to the pathobiology of cervical spondylotic myelopathy. Complementary data in a murine model of cervical spondylotic myelopathy further suggest that targeting the Fas death receptor pathway is a viable neuroprotective strategy to attenuate neural degeneration and optimize neurological recovery in cervical spondylotic myelopathy. Our findings highlight the possibility of medical treatments for cervical spondylotic myelopathy that are complementary to surgical decompression.

Therapeutic cervical medial branch blocks in managing chronic neck pain: a preliminary report of a randomized, double-blind, controlled trial: clinical trial NCT0033272.

BACKGROUND: Based on the criteria established by the International Association for the Study of Pain, the prevalence of persistent neck pain, secondary to involvement of cervical facet or zygapophysial joints has been described in controlled studies as varying from 54% to 67%. Intraarticular injections, medial branch nerve blocks and neurolysis of medial branch nerves have been described in managing chronic neck pain of facet joint origin. OBJECTIVES: To determine the clinical effectiveness of therapeutic cervical medial branch blocks in managing chronic neck pain of facet joint origin and to evaluate the effectiveness of the addition of Sarapin and steroids to local anesthetics. DESIGN: A double-blind, randomized, controlled trial. SETTING: An interventional pain management setting in the United States. METHODS: In this preliminary analysis, data from a total of 60 patients were included, with 15 patients in each of the 4 groups. Thirty patients were in a non-steroid group (combined Group I and II); and 30 patients were in a steroid group (combined Group III and IV). All of the patients met the diagnostic criteria of cervical facet joint pain by means of comparative, controlled diagnostic blocks. Four types of interventions were included. Group I served as control, receiving medial branch blocks using bupivacaine. Group II consisted of cervical medial branch blocks with bupivacaine and Sarapin. Group III consisted of cervical medial branch blocks with bupivacaine and betamethasone. Group IV consisted of cervical medial branch blocks with bupivacaine, Sarapin and betamethasone. OUTCOME MEASURES: Numeric pain scores, Neck Pain Disability Index, opioid intake, and work status were evaluated at baseline, 3 months, 6 months and 12 months. RESULTS: Significant pain relief (> or =50%), and functional status improvement was observed at 3 months, 6 months and 12 months. The average number of treatments for 1 year was 3.8 +/- 0.7 in the non-steroid group and 3.4 +/- 1.0 in the steroid group with no significant difference among the groups. Duration of average pain relief with each procedure was 13.4 +/- 3.5 weeks in the nonsteroid group, and it was 15.9 +/- 8.0 weeks in the steroid group with no significant difference among the groups. CONCLUSION: Therapeutic cervical medial branch nerve blocks, with or without Sarapin or steroids, may provide effective management for chronic neck pain of facet joint origin.

The effectiveness of calcitonin on chronic back pain and daily activities in postmenopausal women with osteoporosis.

The aim of this study was to investigate the effect of nasal calcitonin on chronic back pain and disability attributed to osteoporosis. The study design involved three groups of osteoporotic postmenopausal women suffering from chronic back pain. Group I consisted of 40 women with vertebral fractures, group II of 30 women with degenerative disorders and group III of 40 patients with non specific chronic back pain and without abnormality on plain X-rays. Pain intensity was measured using a numerical rating scale (NRS) and disability due to back pain was measured using the Oswestry disability questionnaire. The patients were randomly assigned to receive, for three months, either 200 IU intranasal salmon calcitonin and 1,000 mg of oral calcium daily (groups IA, IIA, IIIA) or 1,000 mg of oral calcium daily (groups IB, IIB, IIIB). Repeated measures ANOVA showed that there were no significant time, group or interaction effects for pain intensity and disability in any of the groups studied. Mean Oswestry and NRS scores were reduced during the follow-up period in the groups IA, IIIA, but the differences between the two time points were not statistically significant. Intranasal calcitonin has no effect on chronic back pain intensity and functional capacity of osteoporotic women regardless of the presence of fractures, degenerative disorders or chronic back pain of non-specific etiology.

Adverse effects of fluoroscopically guided interlaminar thoracic epidural steroid injections.

OBJECTIVES: To assess the prevalence of adverse effects or complications from fluoroscopically guided thoracic interlaminar epidural steroid injections. DESIGN: A retrospective study with independent observer review. Patients presenting with thoracic radicular pain, caused by either herniated nucleus pulposus or thoracic spondylosis as confirmed by magnetic resonance imaging, received an interlaminar thoracic epidural steroid injection as part of a conservative-care treatment plan. The study was performed in a multidisciplinary spine care center. All injections were performed over a 5-yr period. An independent observer reviewed medical charts, which included a 24-hr postprocedure standardized questionnaire completed by telephone by an ambulatory surgical center nurse. Ambulatory surgical center operative reports and physician follow up office notes up to 3 mos after the procedures, along with epidurograms, were also reviewed. RESULTS: A total of 21 patients who received 39 injections were reviewed. Adverse effects or complications per injection observed included three with increased pain at injection site (7.7%), two with facial flushing (5.1%), one transient nonpositional headache (2.6%), one episode of insomnia the night of the injection (2.6%), and one episode of fever the night of the procedure (2.6%). Statistical analysis revealed no significant difference based on diagnosis (herniated nucleus pulposus vs. spondylosis, P = 0.9156), and age was not linked to higher prevalence of adverse/effects complications (P = 0.3137). CONCLUSIONS: No major complication arose. Adverse effects did occur with a rate of 20.5%. All adverse effects resolved without morbidity. No statistical difference was observed in the rate of adverse effects in patients with herniated nucleus pulposus or spondylosis.

Initial and long-term management of autoimmune neuropathies.

The inflammatory neuropathies (chronic inflammatory demyelinating polyradiculoneuropathy [CIDP], Guillain-Barré syndrome [GBS] and multifocal motor neuropathy [MMN]) affect only one to two individuals per 100 000 of the population, but result in major disability and impairment. Intravenous immunoglobulin (IVIg) can be used as an initial treatment for CIDP, GBS and MMN. While plasma exchange and corticosteroids can also be used initially, they are not as uniformly effective for each of these disorders as IVIg. Substituting corticosteroids, plasma exchange or immunosuppressants may be appropriate for patients not responding to initial IVIg therapy, and combination therapy may be needed in some patients. There are no data from controlled clinical trials of long-term management strategies for CIDP and MMN; however, empirical evidence suggests that a positive long-term response to IVIg can be achieved by increasing the initial dose or its frequency of administration. Corticosteroids and immunosuppressants may be appropriate in some patients with CIDP. Adverse events with IVIg are usually mild and not treatment limiting; however, patients do need to be monitored for uncommon, but serious, adverse events such as renal insufficiency, stroke and thromboembolic events. Nevertheless, the safety profile of IVIg is exceptional relative to the potential complications of other long-term treatments for CIDP and MMN, especially corticosteroids and immunosuppressants. Predictors of response have been reported for each of the neuropathies, and until controlled clinical trials provide evidence on which to base treatment strategies, effective management will require individualising therapy according to patient response.

Effects of Ge Gen Decoction on PGE2 content and COX activity in the degenarated cervical intervertebral discs of rats.

After the rat model of cervical spondylosis was developed for 6 months, the PGE2 content and COX activity in the cervical intervertebral discs were determined respectively by radioimmunoassay and catalytic activity assay. The results indicated that the PGE2 content and COX activity in the model rat increased significantly, and that Ge Gen Decoction could down-regulate the PGE2 content and inhibit COX activity. This is possibly one of the mechanisms of Ge Gen Decoction for treating cervical spondylosis.

Facet, nerve root, and epidural block.

Percutaneous spinal blocks are diagnostic or therapeutic procedures designed to help the neurologist or orthopaedist in their evaluation of confounding low back and/or lower extremity pain. During the initial workup, nonspinal percutaneous blocks, such as hip or sacroiliac joint injection, may be necessary to exclude one of these sites as the origin of the patient's symptoms. Generally, these blocks are safe, quick and easily performed under fluoroscopic guidance. Once the appropriate needle position has been obtained and the short-and/or long-acting anaesthetics instilled into the appropriate site, the patient's response to the block should be documented and transmitted to their referring physician. In the case that the block is successful, the block may be repeated at intervals for pain control, particularly in patients who chose not to have surgery or who are poor surgical candidates. Ultimately, however, as the patient's arthritis and/or disc degeneration progresses, the blocks will become less and less effective and a more permanent solution will be required. This chapter explains the indications, injection options, and methods of performing these various spinal blocks.

Inadvertent subdural spread complicating cervical epidural steroid injection with local anaesthetic agent.

Although cervical epidural steroid injection with local anaesthetic is considered a safe technique and widely practiced, complications may occur. We report a patient experiencing unexpected delayed high block, moderate hypotension and unconsciousness eight to ten minutes after an apparently normal cervical epidural steroid injection. The most probable diagnosis was a subdural block. Anatomical peculiarities of the epidural and subdural space in the cervical region increase the risk of subdural spread during cervical epidural injection. Fluoroscopic guidance is important during cervical epidural injection to increase certainty of correct needle placement, thus minimizing the risk of complications.

[Mydocalm causing anaphylaxis]. / Mydokalm przyczyna wstrzas anafilaktycznego.

The case of anaphylactic shock due to Mydocalm administration is presented. 49-year-old woman suffered from spinal osteoarthritis and she was treated with NSAIDs and Mydocalm for many years. 6 weeks before admission to hospital the first anaphylactic shock was developed with loss of consciousness after oral administration of Mydocalm. Then she was admitted to the hospital in order to diagnose and verify the suspicion whether Mydocalm caused this reaction. Percutaneous test with Mydocalm was performed and it caused anaphylactic shock. Only thirteen cases like this one have been documented in the world literature. It is the first case reported in Poland.

Analgesic effect of etidronate on degenerative joint disease.

In the present study, 80 patients with degenerative joint disease, spondylosis deformans, and/or osteoarthritis of the knee with back or joint pain, especially on movement and strain, were randomly divided into four groups. Group A received no etidronate, while groups B, C and D received 66, 133 and 200 mg/day etidronate, respectively, for 12 months. Every 3 months, after evaluating subjective pain on a visual rating scale (VRS), skin impedance was measured with subjects in a quiet sitting position and with the application of various strains on the spine and knee, including standing up from quiet sitting on a chair, bending forward to flex the spine, squatting to flex the knee, walking 20 paces on a flat floor, ascending 10 stair steps and descending 10 stair steps. A dose related improvement of subjective pain on the VRS with a parallel decrease in the percentage fall in skin impedance was noted. The intra-individual coefficients of variation (CV) of L1-L4 bone mineral density (BMD) on dual-energy X-ray absorptiometry were calculated as a possible index for spondylotic changes before and after treatment as an indication of spondylotic deformity, because no established method is yet available to evaluate such changes objectively. A dose-related decrease in CV of BMD was also noted, parallel to the analgesic effect.

Chronic cervical radiculopathy: lateral-approach periradicular corticosteroid injection.

Thirty-two patients underwent periradicular corticosteroid injections with a lateral percutaneous approach under fluoroscopic guidance, to treat 34 foci of chronic cervical radiculopathy unresponsive to medical treatment alone. The mean evolutionary trends for radicular and neck pain relief were significant at 14 days (P <.001) and at 6 months (P <.001). The procedure did not produce any complications.

[Clinical study on analgesic mechanism of bitongxiao in treating neck pain due to cervical spondylitis].

OBJECTIVE: To study the analgesic mechanism of Bitongxiao (BTX, a Chinese herbal decoction) in treating neck pain due to cervical spondylitis (CS). METHODS: BTX and Jingfukang (JFK) granule were used to treat the treated and the control group separately in 102 CS cases. Plasma leucine enkephalin (LEK), substance P (SP) and prostaglandin E2 (PGE2) before and after treatment were assayed by radioimmunoassay (RIA). RESULTS: Twelve patients in the treated group were clinically cured, 36 markedly effectively, 3 effectively and 1 ineffectively, while in the control group they were 5, 33, 14 and 0 cases respectively. The cured and marked effective rate in the treated group was 92.3%, while that in the control group 72.0%. After treatment the pain score (VAS) of both groups were significantly reduced, but the reduction was higher in the treated group than that in the control. Before treatment, plasma LEK in all patients was abnormally low, but after treatment, it raised obviously more in the treated group than that in the control (P < 0.05). Plasma SP of both groups were obviously elevated, and PGE2 revealed unaltered after treatment. CONCLUSION: BTX has strong, fast-acting and long-lasting analgesic effect with no side-effects, it could elevate the lowered plasma LEK level in cervical spondylitis patients and increase plasma SP level. The analgesic mechanism of BTX might be associated with its effect on LEK, SP or other endorphins, directly acting on the pain modulation system.

A simple and useful method of follow-up after diagnostic and therapeutic injections.

Accurate follow-up after diagnostic and therapeutic injections is extremely important in orthopedic surgery. We describe a simple, inexpensive, and convenient method of obtaining such follow-up in a precise and easy-to-interpret way. A case example is given in which this information was useful to the physician and patient.

Lumbar spine pain originating from vertebral osteophytes.

BACKGROUND AND OBJECTIVES: Axial spine pain originates from a number of structures. Putative pain generators include facet joints, intervertebral disks, sacroiliac joints, and myofascial structures. Osteophytes originating from lumbar vertebral bodies in the area of the intervertebral disks may be a source of nociceptive low back pain which may respond to local injection. METHODS: Five patients with axial low back pain unresponsive to traditional treatment modalities were treated with fluoroscopic guided injection of local anesthetic and corticosteroid near large intervertebral osteophytes. RESULTS: All 5 patients experienced relief. CONCLUSION: Vertebral osteophytes may be a source of axial spine pain. Injection of painful osteophytes with a local anesthetic and corticosteroid solution may produce pain relief.

The efficacy and safety of eperisone in patients with cervical spondylosis: results of a randomized, double-blind, placebo-controlled trial.

A randomized, double-blind, clinical trial was undertaken to assess the activity of eperisone hydrochloride (50 mg t.i.d.), a commonly used muscle relaxant, as a treatment for cervical spondylosis in 157 patients. The results showed a clear benefit of eperisone treatment with regard to pain in the nuchal region, back pain, pain in arms and shoulders, stiffness and other symptoms of cervical spondylosis, while the tolerability of the treatment was optimal.