The Heavy Toll of Prescription Opioids in Terms of Misuse, Abuse, Hospital Admissions & Death

The Back Letter, vol. 24, no. 11, November 2009,
Lippincott, Williams & Wilkins, page 123

The tide of opioid misuse and abuse continues to rise in the U.S. and is taking a terrible toll in terms of injuries and deaths, according to several recent reports. A flood of opioid misuse is fed off the massive increase in the prescription of opioids for the treatment of back and other forms of non-chronic cancer pain in the U.S. that has occurred over the past decade and a half.  The benefits of opioids in the long-term treatment of chronic musculoskeletal pain hasn’t been documented, while the risk related to this treatment experiment are painfully apparent. The National Drug Intelligence Center recently issued a bulletin  in 2009 reporting that an estimated 6.9 million individuals age 12 or older were current non-medical users of prescription psychotherapeutic drugs, including opioid pain relievers, tranquilizers, sedatives or stimulants.  The number of deaths and treatment admissions involving controlled prescription drugs, particularly opioids, increased significantly. 

The number of treatment admissions for prescription opioids as the primary drug of use has increased 74% and intentional overdose deaths involving prescription opioids has increased 114%. 

Among middle-aged adults, drug poisoning has overtaken vehicle-related fatalities as the leading cause of injury deaths in that age group in the most recently studied period. 

92% of poisoning deaths involve drugs.

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Vertebral  Hemangiomas

Eeric Truumees M.D., & Francis H. Shen, M.D.,
Spineline, September-October 2009, 24-30

The authors report a case presentation of an L4 hemagioma with radiculopathy in a 54-year-old female who underwent a hemilaminotomy with attempted decompression after an MRI demonstrated a soft disc.  No plain films had been ordered prior to surgery, and at surgery the procedure was aborted when she lost 4 liters of blood.  She was referred to the radiation oncology department and transferred to interventional neuroradiology for possible biopsy and vertebroplasty. A repeat imaging, which included an MRI, demonstrated diffuse involvement of the vertebral body with apparent preservation of the disc space and some collapse of the superior end plate as well as expansion of the cortex.  There was significant spillage of tumor into the canal demonstrated with stenosis. 

The patient was described as having increased leg pain and weakness and was then referred to a spine surgeon.  Based on the soft tissue spill seen on the MRI, a CT was performed revealing a lytic lesion involving a large portion of the vertebral body with extension into the left pedicle and posterior elements.  There was early collapse of end plates noted, as was ongoing spill of soft tissue into the spinal canal.  A needle biopsy confirmed a highly vascular lesion consistent with a hemangioma. 

Except for its lumbar location, this lesion met all the criteria for an aggressive hemangioma, including involvement of the entire vertebral body, with indistinct cortical margins, irregular honeycomb pattern, soft tissue spill, extension into the posterior neural arch, and a stromal pattern of increased fat and increased vascular contact. 

They noted that with respect to the aggressiveness of this lesion, the patient’s relatively young age of 54, previous failed surgery and neurologic complaints, they recommended a wide resection for decompression and anterior-posterior stabilization.  They also performed preoperative embolization and a 2-inch incision approach was undertaken beginning with a retroperitoneal approach to the L4 level.  Resection of the posterior elements  was performed including right L4 pedicle and cancellous autogenous bone graft harvested through a small cortical window from the posterior iliac crest. The authors presented postoperative images, including 4-month postop CT scans, and there was excellent early growth of the bone graft noted, and slight subsiding of the expandable cage of the inferior L3 end plate was noted immediately after surgery had remained stable. 

They noted the patient did well after surgery despite the size of the surgery and she had less pain immediately in the postoperative period than she did preoperatively.  There was 300 cc of blood loss reported.  The authors note that vertebral angiomas  may involve the epidural space of vertebral bodies. These lesions may be small benign incidental findings or larger more aggressive lesions causing cord compression.  Some have pathognomonic imaging findings and others may be difficult to differentiate from malignant neoplasms. 

They stated that vertebral hemangiomas are common benign vascular tumors identified in 10-20% of specimens in autopsy series. In population-wide plain radiographic surveys, the estimated incidence falls into 10-12% while reporting MRI studies that range from 2.3 to 26.9%, depending on the levels investigated.

These can be found in the upper cervical to the sacral spine and most commonly found in the lower thoracic and upper lumbar spine. 

These lesions are often solitary but up to 1/3 occur as contiguous or non-contiguous multiples, especially in the thoracic spine.

The authors further point out that symptomatic or treated hemangiomas account for only 2-3% of spinal tumors and less commonly patients may present with a syndrome of multiple hemangiomas and may carry an increased risk of progression and therefore might likely become symptomatic. 

They noted that these tumors vary in size and while most are confined to the vertebral centrum, some reach the posterior cortex and less frequently the lesions extend into the surrounding soft tissues, including the spinal canal or into the posterior arch.  Rarely, they affect the posterior elements. 

They stated that women are more likely to be symptomatic.  They can be encountered in any age group, with a peak rise in the fifth decade.  They are rare in children.

They state that the natural history of vertebral hemangiomas is not very well known and are typically referred to as slow growing. They have a variable natural history, however.  Most remain stable over time while others grow quickly.  Radiographically, they can mimic malignant lesions. However, malignant degeneration is uncommon.  They state that certain smaller lesions may require no further evaluation but larger lesions may benefit from serial scanning. 

The authors noted that most commonly the lesions are seen incidentally during evaluation of spinal or thoracolumbar complaints.  They stated that the differential diagnosis should include spinal meningioma, Paget’s disease, multiple myeloma, aneurysmal bone system, and spinal  metastasis.  They stated that these lesions could become symptomatic either by weakening the vertebral body resulting in pathologic fracture or from neurologic compression from fracture fragments or direct compression from the hemangioma itself.  They can become symptomatic because of spontaneous hemorrhage, often without a precipitating event. 

The authors discuss the pathophysiology of hemangiomas and noted that microscopic examination reveals hemartomatous proliferation of vascular tissue with an endothelium lined spaces.  The angiomatous tissue consists of thin-walled vessels and sinuses interspersed among sparsely longitudinal oriented trabeculi and mixed matrix consisting of non-vascular tissues such as fats, muscle and fibrous tissue. 

They discuss the clinical evaluation and the appropriate use of imaging studies, including the specific indications for x-ray, CT, MRI, and spinal angiography. 

They  recommend open surgical decompression to be the procedure of choice for patients presenting with neurologic compromise, which is a type of surgery determined by the location and degree of compression and rate of neurologic decline. They stated that emergency laminectomy is utilized in cases of rapid and progressive neurologic deficit.  They state that due to the high risk for recurrence, patients with significant vertebral body and anterior spinal cord involvement require more radical surgical resection including corpectomy or vertebrectomy.  The discussion also notes that in these cases, there needs to be reconstruction with strut grafts for cages combined with either anterior or posterior stabilization.

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Meeting in Belfast, Northern Ireland

April 30-May 2, 2008,
published in the Journal of Bone & Joint Surgery,
Orthopaedic Proceedings, vol. 91-B2009, supp. III

Five-Year Follow-Up of Neck Pain Patients, Zobivic, et. al, Oxford, United Kingdom, and Dublin, Republic of Ireland

Neck disorders including both neck pain and injuries are a significantly increasing problem worldwide. The purpose of this study was to assess progression of current condition of patients with neck pain 5 years after initial treatment in the back pain screening clinic.  They found significant symptomatic improvement in this cohort group of patients 5 years after initially treated in the back pain screening clinic. Time out of work was significantly increased in patients pursuing litigation compared with patients with spontaneous onset of neck pain. 

Incidence of spinal surgery for patients with back pain, Zobivic, et. al, Oxford, U.K., and Dublin, Republic of Ireland

The purpose of this paper was in reference to a significant problem in Europe and important socioeconomic impact. The purpose of the study was to evaluate the incidence of spinal surgery in patients with back  pain.  The authors found that spinal surgery was not commonly performed in patients with back pain.  The majority of patients have been treated conservatively.  Prior to surgery, nerve root blocks and facet joint injections are useful in selective patients. 

The prediction of good outcomes of spinal surgery with somatized patients, Sell, et. al, Leicester, U.K.

The purpose of this patient was to determine outcomes in somatized patients and identify factors of clinical utility that help predict favorable and unfavorable results. The authors note that somatization is a tendency to experience and express somatic distress in symptoms unaccounted for by pathologic findings and to attribute them to physical illness often in excess of seeking medical help for them.  Somatized patients undergoing spinal surgery have less favorable outcomes than the normal surgical population. However, a range of outcomes occurs. 

They noted traumatic differences existing between somatized patients who have good and poor outcomes following spinal surgery. The number of months from decision to operate to surgery appears to predict good outcomes at 12 months.  No other identifiable preoperative factors were found. 

A comparison between L4-5 and L5-S1 single level discectomy surgery, Sell, et. al, Leicester, U.K.

They found that there was sound biomechanical reason to suspect differences might exist between spinal levels. The L4-5 disc is more susceptible to axial torsion  and was the common site of lumbar instability.  The L5-S1 motion segment is protected from torsional strain by extensive iliolumbar ligaments with more exposure to axial compressive forces.  There appears to be a difference between the L4-5 motion segment and the L5-S1 in outcomes from disc replacement surgery. The available  literature implies the difference but does not include studies with accepted standard outcome measures. 

They found no statistically significant difference between surgery at L4-5 and L5-S1 in terms of postop outcomes. There is no clinically significant difference in the outcomes. Planned surgical treatment strategies should not be altered by perceptions of difference in outcomes when none exists. 

What outcome tools will best suit surgeons in busy low back practices in the era of re-validation and re-licensing?  D’Souza, et. al, Northampton, U.K.

The authors state that U.K. surgeons will need to undergo regular re-validation and re-licensing and as a part of this process will need to collect accurate outcome data.  However, a lack of standardization has led to numerous generic and disease-specific outcome tools being available with increasing complexity in their administration and interpretation.  In research in university settings, these tools are reasonably administered in a busy general spinal practice with limited human and time resources but may not be possible to use reliably and consistently.  Web-based systems remove some of these problems, but data input can be time consuming.

The study evaluates the utility of a subjective patient satisfaction evaluation questionnaire (PSE) by comparing it to well known outcome tools, the Oswestry Disability Index and the Low Back Outcome Score (LBOS). 

They stated that the PSE evaluates pain, the willingness to undergo surgery again in similar circumstances, the likelihood of recommending the operation and undergoing with a friend or family member, and satisfaction of the process of care. Pain relief ranks as good but not complete, little to no pain relief/pain worsened before surgery. The responses are scored 3 points allocated for complete relief of pain, down to none for no relief. The other questions score1 for positive and 0 for a negative response.  The maximum score is 6. Four, 5, or 6 points counts as success as long as the pain component is 2 or 3.  Naught to 3 counts as a failure, as does a score of 4, when pain is related as poor.

The ODI, LBOS, and PSE are not directly numerically comparable but the results can be grouped into success and failure, which gives a basis for comparison from the tools. 

150 consecutive patients who underwent lumbar spine surgery completed the 3 questionnaires independently of the treating surgeon. The scores were subjected to regression analysis and a Pearson’s correlation.  Feedback was sought from the patient regarding the user-friendliness of the questionnaire. 

Results showed a good correlation between the ODI and LBOS with a Pearson value and R-square (rsq) value of 0.86 and 0.75, respectively. The PSE compared to the ODI showing a Pearson value of 0.86 and rsq of 0.74. 

The PSE was found to be a useful and user friendly tool, correlating well with recognized outcome measures, easy to administer, document and interpret. If surgeons with limited resources cannot reliably use a more rigorous outcome tool, using the PSE should provide enough data that can meet the standards required for re-validating and re-licensing. 

Reduction of high-grade adolescent isthmic spondylolisthesis using a 3-stage shortening procedure. Mehdian, et. al, Nottingham, U.K.

Dimensional reduction techniques for high-grade isthmic spondylolisthesis do not address important and anatomic constraints in the L5-S1 nerve roots, thereby leading to a significant risk in neurologic deficit. They describe a novel 3-stage reduction technique carried out in the operating sessions but that respects these anatomic constraints. They report results in 7 cases.  They stated that the safety and efficacy of this 3-stage reduction and stabilization procedure showed that immediate reduction of high-grade spondylolisthesis with minimal risk of neurologic deficit is possible. The procedure is technically demanding and should be performed by spinal surgeons familiar with the principles of anterior and posterior fusion.

They describe the 3-stage procedure, including extensive posterior decompression at L5 and S1 nerve roots, sacral dome osteotomy, anterior L5-S1 discectomy, reduction of spondylolisthesis with pedicle screw fixation and posterior lumbar interbody fusion using interbody cages. 

A prospective comparative cohort study of single level lumbar decompression and an intraspinous distraction device. P. Sell, Nottingham, U.K.

The goal was to compare the outcomes and complications of an intraspinous distraction device in decompression for single-level spinal  stenosis in the lumbar spine. The prospective data were gathered on 2 cohorts of consecutive patients undergoing surgery for single-level symptomatic lumbar spinal stenosis and were matched for age level, surgery, and follow-up. The X-Stop intraspinous distraction device was compared to a standard non-instrumented decompression.

They stated that there is a clinically significant difference in favor of the established procedure of lumbar decompression in terms of improvement in Oswestry disability index in this study. Caution with scrutiny of new implants and procedures is an essential component of clinical judgment and governance.  They stated that there is a clinically significant and statistically significant difference in favor of simple decompression.  They state that the intraspinous distraction group had complications including 3 spinous process fractures and one late migration of implant into the distraction group. There were two incidental dorotomies with epidural bleed greater than a liter in the decompressive group. Six of the intraspinous distraction devices already demonstrated lucent zones around the implant in postop follow-up, the significance of which is not clear. 

Caudal epidural steroid injections for lumbosacral radicular pain: Does it really make a difference?  Swamy, et. al.

They state that the management of radicular pain due to lumbar or sacral nerve root compromise remains controversial.  Caudal epidural injections are widely employed although there is little hard difference to confirm their efficacy.  The empiric treatment still remains a matter of personal choice and experience. They investigate the clinical efficacy of caudal epidural injections and treatment of sciatica and identify potential predictors of response to caudal epidural steroid injections.  They stated that all patients with corresponding radicular pain received a course of 3 caudal epidural injections 2 weeks apart.  They stated that in the largest single series to date, they reported on 628 consecutive patients with 3-month follow-up.  They stated that there was significant improvement in both axial and limb pain in the short and intermediate terms achieved, facilitating onward referral for patient therapy, such as fundamental and optimizing outcomes. They state that long-term follow-up is under way. Sub-groups predicting poor outcome are identified. Positive primary care feedback encourages further recruitment. 

Does the site of the angle or tear influence the site of leg pain? Mehta, et. al, Cardiff, Wales.

They state that radicular pain has been recorded even in the absence of compressive lesion. It has been postulated that annular tears provide a conduit for pro-inflammatory substance which can leak around the nerve root causing radiculitis.  A link between the site of the back pain and site of the angle tear has been reported. The purpose of the study was to establish whether the side or the annular tear may influence the site of the leg in a non-compressive setting.

They studied 121 patients referred with back and radicular leg pain. The mean age was 50 years and 49% were male.  All patients with MRI  demonstrated no compression of the nerve root. They had strict exclusion criteria to exclude patients with neural compression, previous lumbar operation, degenerative deformity, or associated pathology such as peripheral neuropathy.

The annular pathology was described as annular tears and non-compressive disc bulges. The odds ratio for the concurrence of the annular tear causing ipsilateral leg pain is 1.05 and for non-compressive disc bulge causing ipsilateral leg pain 2.14. 

They concluded that a non-compressive disc bulge was more likely to cause radicular symptoms than an annular tear, and both these annular lesions can cause ipsilateral nerve root symptoms. 

High compressive loading of thoracolumbar facet joints leads to osteoarthritis. Adams, et. al, Bristol, U.K.

They stated that osteoarthritis of the apophyseal or facet joints often appears to follow degenerative changes in the adjacent intervertebral disc. The authors tested the hypothesis of facet joints with osteoarthritis and it is directly related to high compressive load resulting from disc derangements. They found that high apophyseal joint loading equivalent to neural arch compressive loading both bearing about 50% is strongly associated with severe osteoarthritic changes in the apophyseal joints.  Associations responded for bone rather than cartilage changes, possibly because pathological load bearing of the facet joints can occur between the tip of the inferior articular process and the adjacent lamina, substantially bypassing the articular cartilaginous surfaces. 

Sacral fractures: Currently strategies in diagnosis and management, Hak, et. al, University of Colorado, Denver, CO.  Orthopaedics, vol. 32, no. 10, October 2009, p. 752-757.

The authors state that while many sacral fractures can be treated non-operatively with restricted weight-bearing, unstable fracture and fractures with associated nerve injuries may require surgical management. 

They state that sacral fractures typically result in high-energy injuries and there is increasing identification of low energy insufficiency fractures with the sacral and pelvis in osteoporotic patients.  The pattern, location, and stability of the fracture vary greatly. Stable non-displaced fractures can usually be treated non-operatively while significant displaced fractures require reduction and internal fixation.

Sacral fractures occur in approximately 45% of all pelvic fractures. They note that the close association of the lumbosacral plexus places the neurologic structures at risk of a traction injury or transection high-energy displaced fractures.  They state that neurologic injuries associated with sacral fractures can range from an incomplete injury of a single nerve root involvement in the entire cauda equina. They state that these fractures can often be difficult to visualize on regular x-rays and improved visualization can be obtained with inlet and outlet radiographs.  They state that surrounding soft tissues often limits image quality. 

They state that a CT scan with coronal and sagittal reconstruction provides optimum imaging to identify and evaluate sacral fractures. They note that MRI, while not commonly required, can be used to evaluate associated neural compromise in selected cases. 

They provide the Denis classification of sacral fractures noting that there are 3 zones. Zone 1’s fractures are lateral to the neural foramina, zone 2 fracture passes through the foramina, and zone 3 fractures are medial to the foramina and involve the spinal canal. 

They also describe transverse sacral fractures as being uncommon and in less than 5% of fractures. However, they did provide a Denis classification for zone 3 fractures, including type 1 fractures showing only kyphotic  angulation of the fracture, type 2 fractures both kyphosis and partial anterior translation, type 3 fractures have kyphosis along with complete translation, and type 4 fractures have segmental comminution of the S1 body  due to axial compression. 

They state that fracture of the sacrum can result in neurologic injury in up to 25% of cases and the nerve injury may involve one nerve root may be unilateral and bilateral depending on the fracture pattern location. The injury can range from neuropraxic injury due to nerve contusion or shearing injury due to transaction to the individual nerve roots, or even complete transection  of the cauda equina.

The L5 nerve root tract traverses the anterosuperior border of the S1 vertebral body and sacral ala and can be injured by fractures in the region during surgical approaches or internal fixation. Sympathetic ganglia of the inferior hypogastric plexus are present along with the anterior surface of the L5 vertebral body and sacrum.  They state that anterior rami of S2 to S5 provide contributions to the parasympathetic nerves that control sex, bladder, and rectal function. 

Associated neurologic injuries, especially of the lower sacral plexus, cannot always be appreciated  unless a thorough examination is performed.  Injuries to the S2 to S5 nerve roots can be easily overlooked since they do not supply motor or sensory supply to the lower leg. S2 innervates the musculature forming the external urethral and anal spincters, S4 and S5 gives sensation to the penis, labia, urethra, prostate, scrotum, and canal. The bladder and rectum are innervated primarily by the pelvic autonomic nerves from S2 to S4. 

Continence and sexual function require at least unilateral preservation of the S2 and S3 nerve roots. The presence of Foley catheter and confounding variables can often initially mask voiding problems, which not uncommonly are attributed to other causes resulting in delayed diagnosis of sacral nerve injury. 

They state that the clinical examination requires more than just a routine examination of the lower extremity sensory and motor  function. They state that additional examination was required to identify injuries of lower sacral plexus. A rectal examination must be performed to evaluate sphincter contraction and to exclude an open pelvic fracture. Light touch and pinprick sensation should be assessed, whether perianal dermatomes of S2 to L5, in addition to perianal wink, bulbocavernosus, and cremasteric reflexes should be assessed. 

The location of the fracture is predictive of neurologic injury. The zone 3 fractures are less frequent and associated with the highest rate of nerve injury.  In a retrospective review of 236 fractures, Denis noted that 57% of patients with zone 3 injuries had a neurologic deficit while the zone 1 injuries were the most frequent and had the lowest rate of associated nerve injury. 

They describe  surgical fixation techniques including the use of percutaneous iliopsoas screws, posterior sacral tension band fixation, lumbopelvic fixation, and triangular osteosynthesis. 

They describe neural decompression which may be required directly through a laminectomy and foraminotomy.  They stated that 80% of initial nerve injuries may improve regardless of treatment. Nerve injury due to neurapraxia due to fracture translation, angulation, or direct compression has a good chance for recovery.  Nerve transection of nerve  root avulsion is less commonly seen but offers good prospects for recovery. 

They emphasize the relative ease with which sacral fractures and associated neural compromise can be missed on initial evaluation of the trauma patient necessitating the examiner maintain a high index of suspicion.

Again, appropriate imaging including CT scanning is important, but these studies are not a replacement for a very thorough and complete neurologic examination. 

Neutrophil CD64 expression in the diagnosis of local musculoskeletal infection and the impact of antibiotics.  S. Tanaka, et. al, University of Tokyo, Department of Orthopaedic Surgery, Tokyo, Japan.

This research group examined the usefulness of neutrophil CD64 expression in detecting local musculoskeletal infection and the impact of antibiotics on this expression. Of 141 patients suspected of musculoskeletal infection, 46 were confirmed by microbiological culture to be infected  and 95 had infections excluded.  The median CD64 count of patients with localized infection was 2,230 molecules/cell, and that of a patient without infection was 937 molecules/cell.  The level of CD64 correlated with the CRP level in patients with infection, but not in those without infection.  The receiver/operator characteristic curb analysis revealed that CD64 is a good predictor of local infection.  When the patients were subdivided into two groups based on the administration of antibiotics at the time of CD64 sample, the sensitivity per detected infection was better in those not receiving antibiotics. These results suggest that the measurement of CD64 expression is a useful marker for local musculoskeletal infection. They note that infection in musculoskeletal surgery results in morbidity and mortality but also poses an enormous socioeconomic burden on society. An early and accurate diagnosis of local infection remains a major challenge for clinicians to improve prognosis and reduce costs.  However, clinical symptoms such as pain, swelling, redness, and local increase in temperature are not sufficient or specific to confirm infection. 

General inflammatory markers such as a level of CRP and ESR in the white blood cell are diagnostically useful but again lack specificity.  Although a positive microbiological culture  is regarded as the absolute arbiter, the technique is time consuming and sometimes results in false-negative results. The rate of 2 positive results from microbiological culture has been reported to 40% to 65% in the case of local infection. 

CD64 is an FC receptor for IgG, commonly known as F gamma receptor 1 (FC gamma R1).  It plays a role in antibody dependent cytotoxicity, for clearance of immune complexes in the phagocytosis of targets opsonised with IgG and medicates the release of pro-inflammatory cytokines, such as interleukin-1 (IL-1), IL-6, and tumor necrosis factor-A alpha (TNF-alpha). 

CD64 is constitutively expressed on macrophages, monocytes, and eosinophils and is upregulated on neutrophils as a physiological response to components of the microbial wall, such as lipopolysaccharides, complement split products, and some cytokine, such as interferon-gamma, IL-8, IL-12, and granulocyte colony stimulating factors.

In terms of infection, CD64 expression has been reported to be induced not only by bacteria but also by viruses and Mycobacteria. 

It has been previously reported that the quantitative measurement of CD64 expression on the surface of neutrophils is a sensitive and specific marker of systemic infection, even in patients with systemic inflammatory disease. We have therefore examined the usefulness of neutrophil CD64 expression in the diagnosis of musculoskeletal infection and the impact of antibiotics on the predictive values of CD64. 

The authors thereby conclude that the level of neutrophil CD64 expression is helpful in confirming the presence of musculoskeletal infection and although the administration of antibiotics before its measurement produces its negative predictive value, it still appears to be a better predictor of local infection than CRP, ESR, and/or the white blood cell count. 

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Pathophysiology & biomechanical implications of ankylosing spondylitis in the spine.

Nicholas Szerlip,
M.D., & Charles Schnee, M.D.,
University of Maryland School of Medicine. Spine Line,
July/August 2009, pp. 16-21

Ankylosing spondylitis is a seronegative systemic inflammatory disease affecting many body systems. The most relevant to spine specialists is the manner in which it infects the spinal column. The basic pathology in AS is caused by generalized paravertebral ossification of bridges of vertebral joints, the costotransverse joints, and the sacroiliac joint. It is characterized by inflammation of partial ossification of the ligament, intervertebral disc and plates, and zygapophyseal joints. Understanding the disease’s basic molecular components all house a better understanding of how and why the spine is affected. The distinct genetic susceptibility of AS in the role of HLA-B27 as well as other antigens are discussed.

AS alters spinal biomechanics, increasing fracture deformity and risks. When fracture occur, a 3-column ossification confers a significant risk for instability and delayed neurologic deficit in undiagnosed and inadequately stabilized fractures. Patients with AS should be advised to seek medical attention immediately after trauma.

Spinal and pulmonary manifestations predominate but the eyes, heart, and kidney may be affected. In the general population, AS has a prevalence of about 1%. Commonly seen in young adults, the average age of diagnosis is 24. Each individual has unique presentations. Symptoms vary from intermittent recurrent spinal pain to a disabling chronic affliction affecting not only the spine but peripheral joints and other organ systems, resulting in severe loss of motion and deformity. Men seem to be predisposed to spinal pathology while appendicular involvement is more common in women. Patients with symptomatic AS frequently become disabled, use substantial health care resources, realize reduced earnings, and experience an impaired quality of life.

Decompression during surgery is necessary if stenosis persists despite restoration of alignment in the incomplete patient. In particular, preoperative advanced imaging should be carefully assessed for the presence of associated traumatic spinal epidural hematoma that may require evacuation. Most fractures can be treated with a posterior instrumented fusion. Additional points of fixation rostrally and caudally are necessary given the long lever arms and the often compressed osteoporosis. Spinous process wiring and laminar hooks can be used for additional fixation. If the ventral column is substantially compromised, combined anterior and posterior reconstruction and instrumented fusion may be necessary.

AS alters spinal biomechanics and predisposes patients to fracture and deformity. A post inflammatory response leads to ossification hovering around and ultimately ankylosing the spine.

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Diagnosis & management of lumbar spinal stenosis

Andrew Haig, M.D., and Christy C. Tompkins,
Ph.D., University of Michigan, Department of Physical Medicine & Rehabilitation,
JAMA, January 6, 2010, vol. 303, no. 1

The diagnosis of lumbar spinal stenosis defined as a clinical syndrome of buttock or lower extremity pain, which may occur with or without back pain associated with diminished space available of the neural and vascular elements of the lumbar spine is an important driver of the exponential increase in the number of fusion procedures performed on elderly people over age 60. They estimate that 90 of 100,000 persons older than 60 undergo this procedure annually.

They state that most surgeons rely on imaging or diagnosis of spinal stenosis to determine the need for surgery. The authors point out, however, the assumption that radiologic measures which confirm the diagnosis of a clinical  syndrome of stenosis has been questioned.  They state that without a clear diagnostic standard, a management strategy to minimize the potential of harm from an incorrect diagnosis needs to be developed. 

They state that there is a lack of clear relationship between imaging findings and clinical presentation in spinal stenosis and also that imaging studies are conducted with patients supine, whereas symptoms of stenosis are generally precipitated by standing or walking.  The authors point out that with upright positions, the spinal canal can be made smaller by segmental instability, compression by soft tissue structures such as facet joint syndrome, ligamentum flavum, intervertebral disc, and posterior epidural fat, or venous congestion. 

They suggest that when evaluating older patients with suspected spinal disorders, it is necessary to define and treat what is not stenosis,  define and treat the effects of stenosis, and treat the stenosis without a definitive diagnosis.  Failing all of these tests, positive diagnosis is an important consideration before surgery.  They state that with respect to treating what is not stenosis, the presence of leg pain does not necessarily mean that clinically the most relevant symptoms are the result of nerve root compression.  A mechanical back pain is ubiquitous, persons who have leg disorders ranging from diabetic neuropathy, peripheral vascular disease, and polyarthritis may be diagnosed as having spinal stenosis.

The back pain component of clinical stenosis may result from mechanical pain generators such as sacroiliac joints, facet joints, hip joints, trochanteric bursitis, or gluteus medius tendons. 

Surgery to treat stenosis might have an inadvertent positive effect on mechanical pain generators. However, most physicians would advocate a conservative approach to these structures. 

Patients with back pain may have other reversible disorders that are more important or that exacerbate pain and functional limitations associated with stenosis.  Depression, deconditioning, and obesity are frequently reversible constitutional causes of disability in persons with spinal disorders. Treatment of stenosis in persons with activities limited by osteoarthritis, cardiopulmonary disease, or social barriers may add little to the quality of life. 

They state that secondly one should define and treat the effects of stenosis. Compared with younger persons, older patients with disabling back pain are more compromised in most aspects of function and quality of life.  However, their disability may be unrecognized because they may rate their perceived physical and mental health as similar to that of younger persons.  Multi-disciplinary rehabilitation is an established but often overlooked treatment for chronic back disability. 

The authors note that older patients respond positively to exercise, including strength, endurance, flexibility and coordination, in addition to counseling, lifestyle modification and environmental modification.  Some patients with neurogenic claudication will opt for  adaptations such, as  electric scooters, rather than surgery.

With respect to their third recommendation, they state to treat the presumed diagnosis without a definitive diagnosis.  To date, only a handful of published randomized controlled trials have evaluated non-invasive treatment for spinal stenosis.  However, this does not eliminate treatments such as physical therapy, spinal injection, and medication, which all should be considered. 

The authors  point out that physical therapy is an accepted treatment for spinal disorders in general. A wide range of physical therapy related treatments have been advocated for patients with stenosis, including exercise and lumbar flexion, such as cycling, body weight supported treadmill walking, aggressive walking to the point of claudication, muscle coordination training, lumbar semi-rigid orthoses, braces and forceps, pain relieving modalities such as heat, ice, electrical stimulation, massage, and ultrasound, and manual medicine treatments such as postural instruction. 

The authors discuss epidural steroid injections which ordinarily present minimal risk and may have potential benefit and may be tried before surgery if surgery is considered.  One approach is to use transforaminal technique targeted to the most clinically affected nerve roots and add an injection to the adjacent facet joint to decrease inflammation of a nerve foramen wall.

The authors note that medication is not the initial therapy that physicians should consider for chronic back pain.  They describe a comprehensive review noting that at best, drugs relieve only approximately 30% of chronic pain.  They describe the risks that older patients face, who are taking pain medication, which include the risk of falls, cognitive deficits, constipation, bladder dysfunction, and adverse drug interactions. 

They add that one should consider time as an important treatment for spinal stenosis and they note that spinal stenosis is not a condition of instability but is a stable disorder. They state that patients who develop serious disability and neurologic deficits usually do so over time and the decline is not predicted by pain levels or imaging abnormalities.  They state that the decision for treatment should be based on the current pain and disability and not by anticipating a  future problem. 

They advocate making a positive diagnosis  of stenosis and initiating conservative approaches that may resolve symptoms for many patients, and for the remaining patients, they also note that mechanical pain generators and unrelated causes of disability should be treated or optimized and reversible consequences of stenosis should be managed or understood. 

They state that for patients in significant distress despite physical therapy, injections, medication, time, or an EMG has ruled other causes of nerve pain, imaging is useful in planning operative care. 

They state that surgery under these circumstances can be a thoughtful deliberate intervention that should help to reduce pain and increase activity and increase quality of life. 

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“Radiographic Predictors of Clinical Outcomes Following Operative v. Non-Operative Treatment of Degenerative Spondylolisthesis”

Adam Pearson, M.D., et. al
Spine Journal 8 (2008, 1S-191S)

Proceedings of the 23rd Annual Meeting of
the North American Spine Society,
October 15-18, 2008.

This study was performed in order to evaluate whether baseline radiographic findings predicted outcomes in patients with degenerative spondylolisthesis.  The outcome measures utilized were in SF-36 bodily pain (BP) and physical function (PF) scores, Oswestry Disability Index (ODI), and Stenosis Bothersomeness Index (SBI).  They found that overall, surgery patients improved more than patients treated non-operatively.  Regardless of the grade of spondylolisthesis, disc height or mobility, they found that patients who had surgery improved more than those treated non-operatively.  They also reported that surgical treatment effects were greater for grade 2 patients than for stable patients.  This difference was due in part to differences in non-operative outcomes which were better in patients classified as grade 1 or hypermobile. 

This same study group presented another paper entitled “Spinal Stenosis v. Degenerative Spondylolisthesis: Comparison of  Baseline Characteristics & Outcomes.”  They found that spinal stenosis and degenerative spondylolisthesis patients had similar baseline characteristics, but spinal stenosis patients improved less with surgery than degenerative spondylolisthesis patients.  These differences in surgical outcomes may be related to underlying different disease processes, different operative treatments, or both. 

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“Curve Regression in Idiopathic Scoliosis:
A Follow-Up Study to Skeletal Maturity”

Ken-Jin Tan, et. al
Spine, 2009; 34: 697-700

The authors recognized that the care of adolescents with mild curves because of idiopathic scoliosis is a constant clinical dilemma.  Management decisions should ideally be based on accurate prediction of long-term curve behavior and not on risk for a curve progression or defined magnitude over a shorter duration of skeletal growth. 

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Degenerative Annular Changes Induced by Puncture
are Associated with Insufficiency of Disc Biomechanical Function

Adam H. Hsieh, et. al,
Spine, 2009; 34:998-1005

The authors developed a study to determine immediate biomechanical effects of annular injury by needle puncture.  Their findings suggest that injury size is large enough to disrupt biomechanical dysfunction or needed to drive degenerative changes in rat caudal disc annular fibrosis.  They reported that small annular defects become sealed, allowing the disc to function normally, and the annulus fibrosis to heal, but larger defects appear to require longer wound closure times and may prolong the duration of impaired disc function.  They observe that puncturing discs with an 18-gauge needle significantly compromised the behavior of the disc due apparently to extrusion of the nucleus pulposus, and this was statistically associated with induction of degenerative annular changes in people.  They reported that induction of these morphologic changes depended on the size of the defect being large enough to affect disc creep behavior.  They found that 22 or 26 gauge percutaneous needle punctures in rat caudal discs did not induce degenerative changes. 

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“Effectiveness of Physical Therapy & Epidural Injections in Lumbar Spinal Stenosis”

Zarife & Koc
Spine, 2009; 34: 985-989

The authors studied the effects of epidural steroid injections and physical therapy on pain and function in  patients with lumbar spinal stenosis.  They do acknowledge that there is a lack of sufficient data concerning the effectiveness of conservative treatment in lumbar spinal stenosis.  They studied 3 groups of patients. The first group received inpatient physical therapy, the second group received epidural steroid injections, and the third group were controls.  All 3 groups received diclofenac and a home-based exercise program.  They reported significant improvement in the epidural steroid and physical therapy groups in pain and function parameters and no significant difference between the 2 groups.  They found that the epidural steroid injections and physical therapy groups demonstrated some level of improvement up to  6 months in follow-up.  They noted that lumbar spinal stenosis is one of the most common degenerative spinal disorders in the elderly population, and common factors contributing to this problem include degenerative changes with the facet joints and also ligamentum flavum hypertrophy, disc degeneration, spondylolisthesis, and scoliosis.  They reported ischemia, cauda equina, or spinal nerves play a role in the pathogenesis of these symptoms.  They doubt that symptoms of stenosis include low back pain and lower leg complaints including pain and numbness and weakness, and symptoms vary with postural change as extension causes a decrease in foraminal dimensions and flexion has the opposite effect.  They support MRI as useful for the assessment of severity of stenosis by enabling spinal canal diameter measurements. 

They recommend initial treatment focus on patient education, pain control, exercises, and physical therapy and in patients  who do not improve with conservative care to consider surgery.

The authors also acknowledge that the underlying mechanism of action of epidural steroids and local anesthetic injections is not well understood but that it is thought that this achieves neural blockade, which alters or interrupts nociceptive input, reflex mechanisms induced by afferent fibers, self-sustaining activity of the neurons, central neuronal.  The authors do point out that corticosteroids reduce inflammation via inhibiting pro-inflammatory mediators causing a reversible local anesthetic effect. 

They do readily admit that the efficacy of epidural steroid injections, prospective, randomized controlled studies are lacking for the treatment of lumbar spinal stenosis.  They conclude by stating that epidural steroid injections provide better improvement in the short term. 

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Clinical and Biomechanical Evidence Validating
Pain Centralization and Directional Preference
Ronald Donelson, MD, MS
SelfCare First, LLC

DEFINITIONS OF CENTRALIZATION AND DIRECTIONAL PREFERENCE
For patients presenting with lumbar or cervical pain, the centralization phenomenon (CP) and
directional preference (DP) are often identifiable in patients’ histories and then elicited and
observed during a specialized clinical exam using repeated end-range test movements, as
described by McKenzie as part of a paradigm of care that has come to be known as Mechanical
Diagnosis and Therapy (MDT). CP is characterized as a prompt retreat of any radiating or
referred pain back to the lumbar or cervical center or midline, which is routinely followed by
elimination of that central pain as the result of performing a single direction of repeated endrange
lumbar testing.21 This specific change in pain location can occur with flexion, extension,
or laterally-directed testing. There is typically only a single direction of testing that elicits this
unique pain response and that direction is referred to as the patient’s “directional preference”.

CP AND DP PREVALENCE
When this specialized examination is conducted by clinicians well-trained in MDT methods of
examination, the prevalence of CP and DP in the LBP population is surprisingly high, reported
as 70-89% in those with acute LBP and 32-52% in those with chronic LBP.5-8,13,16,18-20,29,32,34

CP AND DP RELIABILITY AND OUTCOME VALIDITY
There are now many studies focused on CP and DP that report positive findings in three
important areas of research:

1. high reliability in identifying DP and DP and the large subgroup
of LBP patients those two clinical findings characterize;3,4,10,11,14,23,30,34,35

2. CP and non-CP findings are strong predictors of excellent and poor outcomes respectively;8,12,13,16,19,29,31‐34 and

3. DP-specific treatments, consisting of directional exercises and posture strategies, consistently
produce good-to-excellent outcomes, demonstrated in many cohort8,12,13,16,19,29,31‐34 and now five randomized clinical trials. 1,2,15,20,25

A PATHOANATOMIC MECHANISM FOR CP AND DP?
An additional form of validation of the CP/DP subgroup has emerged linking these CP and DP
findings to symptomatic disc pathology. This includes both acknowledged forms of disc pain:
sciatica due to herniated nucleus pulposus (HNP) and internal disc disorders. A substantial
percentage of patients with sciatica has been shown to have a DP, meaning their leg pain
“centralizes”, or retreats out of their leg to the center of their back, during their baseline testing
assessment.16,20,29 They then routinely report excellent outcomes when treated with directional
exercises and posture modifications that match their DP. One study of 67 patients, all with
sciatica and neural deficits and were facing surgical disc excision, reported that 52% were found
to have an extension DP, i.e. their leg pain centralized during their initial evaluation.16 By
performing extension exercises several times each day, every one of them was able eliminate all
their symptoms and restore their full lumbar range-of-motion within five days. None of those
required surgery.

The second form of disc pain related to internal disc issues is identifiable only with discography,
a controversial imaging study. However, two studies report similar findings in chronic LBP
patients: there was a strong correlation between discography findings and whether or not those
patients could centralize their pain during a pre-discographic MDT assessment.5,18 One study
reported CP had a 100% specificity in making a pathoanatomic diagnosis of internal disc
disruption (i.e. discogenic pain) based on discographic findings in subjects not distressed or
severely disabled, and an 80-89% specificity for distressed or severely disabled individuals.18

Such high specificity enables identification of a large subgroup of chronic LBP patients with
internal disc disruption who also, according to a large number of cohort and RCTs, have an
excellent chance of rapid recovery with non-surgical treatment that is focused on directionspecific
exercises and posture strategies. This further begs the question of how many chronic
axial pain patients have an undiscovered DP, and therefore an excellent prognosis, but instead
undergo an unnecessary spinal fusion or disc arthroplasty justified by their positive discogram
rather than providing them with the opportunity to be evaluated using MDT principles that would
identify their DP?

Meanwhile, a large number of biomechanical studies of internal disc dynamics have clearly
established that normal disc nuclei move posteriorly within the disc with lumbar flexion loading
and then move back anteriorly with subsequent extension loading.9,17,22,24,26-28 Such a directional reversal of nuclear displacement precisely matches the reversible symptomatic response that accompanies intentional directional loading tests to elicit CP and DP during this MDT assessment. This directional nuclear displacement model explaining CP and DP would relate to both the internal disc pain as well as external nerve compression forms of disc pain.

A recently published study provides additional insight into the validity of a directionally
reversible pain-generating disc pathology accounting for DP and CP. 24 Wishing to investigate
mechanisms by which CP and DP clinical findings could be linked to a painful intervertebral
disc, the investigators asked: could posteriorly displacement of nuclear material produced by
repeated flexion loading be reversed and returned to its central location within the disc simply by
applying repeated extension loading to the disc?

Eighteen porcine C3-4 cervical spines were dissected and potted in cups and then repeatedly
loaded in either pure flexion or combined flexion and side flexion at a rate of 0.5°/s. Eleven of
those specimens prolapsed and were then loaded repeatedly in pure extension. The authors
quoted independent sources that acknowledged the close biomechanical similarities between the
porcine cervical discs and human lumbar discs.

The prolapsed nucleus was successfully reduced in 5 of the 11 specimens as a result of this
extension reversal testing. The remaining six did not change. Those that reduced had greater
disc space height than those that did not, while neither the morphology of the herniation
(circumferential or radial) nor the angle of lordosis of the specimens predicted their response to
extension loading.

The investigators concluded that disc prolapse from repeated flexion could be reversed and
directed back toward the center of the disc, in this case by a direction of bending and loading that
was directly opposite to the direction of loading that produced the prolapse.

CONCLUSION
This biomechanical evidence that reversing the directional loading on a displaced disc nucleus is
a close, if not precise, match with the centralizing pattern of pain response seen so often when
patients perform repeated lumbar end-range extension testing in symptomatic lumbar or cervical
patients. This disc displacement/reduction model also nicely fits both recognized models of disc
pain production which may explain the very high prevalence of DP and CP reported in so many
studies. It is becoming quite defendable that CP and DP may identify patients whose pain is
caused by some degree of excessive nuclear displacement and in whom a mechanism for
reducing that displacement can be found, whether the pain is caused by the displacement merely
irritating posterior anular nociceptors or is being generated by nerve root compression from an
HNP.

As further research unfolds, if this reversible nuclear model proves to be the mechanism by
which so many patients develop and can then centralize their pain with a DP (70-89% of acute
LBP), it would suggest that disc pathology is the dominant underlying LBP generator, regardless
of whether the pain is limited to the low back or radiates to full sciatica.

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Neuralgic Amyotrophy
S. Sathasivam, B. Lecky, R. Manohar, A. Seelvan
Walton Center for Neurology and Neurosurgery, Liverpool, England
J. Bone Joint Surg (BR 2008; 90-B: 550-3)
Volume 90-B, #5, May 2008

Neuralgic amyotrophy is an uncommon condition, characterized by the acute onset of severe pain in the shoulder and arm, followed by weakness and atrophy of the affected muscles and sensory loss as the pain subsides.  The diversity of its clinical manifestations means that it may present to a variety of different specialties in medicine.  This paper described the epidemiology, pathogenesis, clinical features, differential diagnosis, investigations, treatments, course of prognosis. 

The authors state that there is a diversity of presenting features.  They state that neuralgic amyotrophy has been referred to in the past as Parsonage-Turner syndrome, acute brachial neuropathy, acute brachial plexitis, brachial plexus neuropathy, cryptogenic brachial neuropathy, idiopathic brachial plexopathy, idiopathic brachial neuritis, localized neuritis of the shoulder girdle, multiple neuritis of the shoulder girdle, paralytic brachial neuritis, serum neuritis, shoulder girdle neuritis in the shoulder girdle syndrome. 

They state that this condition may be a result of an autoimmune process. A study has demonstrated that lymphocytes of patients with this condition increase their blastogenic activity in cultures with nerve extracts from different nerves of the brachial plexus and their branches, but not on cultures with extracts of nerves from the sacral plexus.  An additional study demonstrated increased compliment fixing-antibodies from peripheral nerve myelin in the acute phase of three patients with neuralgic amyotrophy. 

They state that the hereditary form of the condition is an autosomal dominant recurrent neuropathy affecting the brachial plexus.  There has been observed mutations in the gene septin-9 on chromosome 17Q25 in several families with hereditary neuralgic amyotrophy.  They state that gene septin-9 is a member of the cytoskeleton-related septin family which is highly expressed in glial cells in neuronal tissue. 

The characteristic presentation is an acute severe burning in the shoulder or arm lasting for several days or weeks followed by muscle weakness, atrophy and sensory loss as the pain diminishes.  This condition may also occur bilaterally in the upper extremities.  The pain is usually in the shoulder, and can radiate from the shoulder to the arm, from neck to the arms, scapular or posterior chest wall region, anterior chest wall or both.  It is typically severe and unrelenting and can wake patients from sleep.  It is commonly worsened by movement of the shoulder or arm resulting in patients holding the arm with the elbow flexed and the shoulder adducted. A distinguishing clinical point to distinguish it from cervical radiculopathy is that neuralgic amyotrophy is not aggravated with the Valsalva maneuver.  The pain can last up to eight weeks. 

Commonly affected are the infraspinatus, supraspinatus, serratus, anterior biceps, deltoid and triceps.  Nerve involvement can include the anterior interosseous branch of the median nerve.  Phrenic neuropathy may occur causing paralysis of the diaphragm, and usually hemidiaphragmatic. 

There is frequently seen sensory involvement and most often over the deltoid and lateral aspect of the upper arm and the radial side of the forearm. 

There may be autonomic signs as well including trophic skin changes, edema, temperature dysregulation, increase sweating and change in nail or hair growth which occurs in as many as 15% of patients.  Rarely a Horner syndrome may occur.   

Blood tests may reveal elevated liver enzymes and positive antiganglioside antibodies.  Cerebral spinal fluid may on occasion reveal mildly elevated protein, slight pleocytosis and oligoclonal bands.  A chest x-ray may detect an elevated hemidiaphragm caused by involvement of the phrenic nerve. 

An MRI may reveal abnormalities in the musculature of the shoulder girdle related to denervation.  There may be changes in the signal intensity of muscles on MRI.  The intensity may be normal in the acute phase of denervation.  There may be detectable changes in denervated muscles with a diffuse increase of the T2 weighted signal as a result of edema without a T1 weighted change.  Muscle atrophy may develop.   Muscle atrophy on an MRI could reflect an increase in the intramuscular linear T1 weighted signal because of fatty infiltration which may return to normal several months after the chronic stage.  An increased T2 weighted signal in the supraspinatus, infraspinatus and deltoid at initial presentation and T1 weighted change of atrophy without fatty infiltration during follow-up have been reported in three cases.  

With respect to muscle changes, the most commonly involved would be considered the supraspinatus, infraspinatus, deltoid and teres minor. 

MRI of the brachial plexus is not sensitive enough to be reliable.  Magnetic resonance neurography, however, may reveal, in the acute phase, a thickened and hyperintense brachial plexus and in the chronic phase may reveal hyperintensity.

Electrodiagnostic studies may reveal a proximal conduction block, although the primary pathology is thought to be axonal degeneration.  There may be a complete resolution of the block within nine months suggestive that in some cases demyelination may predominate in the early stages.  Occasionally one may see a delayed distal latency and a decreased amplitude of compound muscle action potentials.  Within three to four weeks after the onset of symptoms, EMG may reveal acute denervation indicating axonal degeneration with positive sharp waves and fibrillation potentials three to four weeks after the onset of symptoms.  Chronic denervation may be revealed with early re-innervation with polyphasic motor unit potentials within three to four months.

Treatment for this condition may include corticosteroids, analgesics, and physical therapy.

Recovery is seen in most patients within two to three years.  Some patients may have persistent pain or weakness after six years.  Recurrence may occur in 5% to 26% of patients. 

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Thoracic Spine Pain In Youth:
Should We Be Concerned?
The Spine Journal (April 2009, volume 9, #4, 338-339)
This was a letter to the editor from
Dr. Andrew Briggs, Ph.D., and Leon M. Straker, Ph.D.

Spinal pain in adolescents is not trivial and represents a cause for concern.  Evidence is now emerging, which highlights an alarmingly high prevalence of spinal pain in youth and suggest that spinal pain is becoming more common.  They state that sources of thoracic spine pain may include spinal structures, the thorax, and the GI and cardiopulmonary and renal systems.  The thoracic spine is a common site for inflammatory, degenerative, metabolic infective and neoplastic conditions that may also contribute to pain and disability. 

The authors point out that the benign thoracic spine pain is a common presentation in clinical practice.  They further state that nonspecific thoracic spine pain is also prevalent.  They note that this may be mediated by a combination of physical and psychological factors similar to other musculoskeletal pain conditions.  They note that examples of physical factors would include biomechanical loading, and psychosocial factors would include stress and depression.  The authors state that compared with the neck and low back, the thoracic spine has received less attention.

The author recommended that perspective cohort studies designed to specifically address thoracic spine pain are needed to elucidate the impact of the condition and its modifiable physical, psychosocial and lifestyle related risk factors. 

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The Pharmacological Management of Skeletal Related Events for Metastatic Tumors. 
A. Hitron Pharm.D. and V. Adams Pharm.D.
Orthopedics (March 2009, Volume 32, #3)

Since the mid-1990s, bisphosphonates have become a mainstay of the management of metastatic bone disease from breast, lung and prostate cancer.  They are the primary treatment of hypercalcemia, widely recommended to reduce the pain associated with metastatic disease and are the only class of agents approved to prevent the development of skeletal-related events.  Bone is one of the most common sites of metastatic disease in patients with cancer, affecting approximately 400,000 patients each year.  nearly 70% of patients with advanced breast or prostate cancer will experience bone lesions; 50% of these patients will develop a secondary skeletal complication.  Skeletal infiltration is also frequently found in patients with multiple myeloma, thyroid, kidney or lung disease.  The pathologic penetration of bone by tumor tissue can lead to numerous skeletal-related events such as hypercalcemia, fracture, spinal cord compression and potentially debilitating bone pain.  often these consequences result in the need for radiological and surgical intervention.  Along with these therapies, pharmacological management is required to help reduce symptoms, prevent recurrence and further improve patient’s quality of life. 

More recent studies have demonstrated how metastatic lesions develop once cancer cells reside in the marrow.  Cellular moderators such as Receptor Activator for Nuclear Factor kb Ligand.  Parathyroid hormone-related protein and serine protease urokinase disrupt the balance of osteoblast and osteoclast activity that are involved in the formation of metastatic lesions.  Most bone lesions are classified as osteolytic or osteoblastic, depending on the direction of the bone breakdown/rebuilding imbalance.  In osteoplastic lesions, such as prostate cancer metastasis, the production of endothelin-1, transforming growth factor-B and UPA directly increase osteoblast activity and the formation of space occupying bone lesions.  In osteolytic lesions, primary breast and lung cancer metastasis, osteoclast activities increase with the production of PTHRP which stimulates Nuclear Factor kb from stromal cells of bone, leading to increased osteoclast differentiation and activity. 

Numerous studies have also shown that this activity that occurs in the marrow in both osteolytic and osteoblastic lesions also may lead to increased tumor proliferation.  As osteoclast break down bone, growth factors are released to stimulate the production of osteoblast, allowing for bone repair and remodeling.  These factors including TGF-B platelet derived growth factor have been shown to perpetuate bone metastasis in both breast and prostate cancer models. 

They state that in nearly one-third of patients with bone metastasis, pain is caused by pathologic fracture.  Similar to osteoporosis, this is often caused by lytic breakdown of bone often the ribs, spine and long bones.  Pain is the most common symptom of fracture, although some patients may develop kyphosis from compression of the spine. In approximately 6% of patients fracture may lead to the development of neurologic symptoms.  Spinal cord compression is also another cause of neurologic symptoms in patients with metastatic bone disease. 

Hypercalcemia is another common presentation of skeletal metastasis.  Hypercalcemia can occur from metastatic disease or from parathyroid hormone imbalance.

Bisphosphonates are the primary treatment of hypercalcemia, widely recommended to reduce the pain associated with metastatic disease and are the only class of agents available to prevent the development of skeletal-related events.  These agents function to inhibit osteoclast activity by binding to the bone matrix, where they are internalized by osteoclast leading to osteoclast dysfunction and apoptosis. 

Oral clodronate, one of the first agents tested was found to significantly increase the time to skeletal-related events.  Since the testing of clodronate, newer more potent agents have been developed.  Pamidronate (Novartis), Aredia, and Zoledronic acid have been shown to be efficacious in the reduction of skeletal-related events for metastatic disease and are currently the only agents FDA approve for this indication. 

In a randomized placebo controlled trial of 382 patients with breast cancer during a two-year period, Pamidronate was found to reduce the risk of skeletal-related events by 50-70% in 24 months.  Additionally, patients on Pamidronate experienced a statistically significant decrease in pain. 

There is no significant difference found between Zoledronic acid versus Pamidronate. 

The authors state that corticosteroids are used most commonly in patients that develop spinal cord compression but may also be used in those with diffuse pain unresolved with bisphosphonate and analgesic use.  They are considered as potent anti-inflammatory agents. 
They state that opioid and nonopioid analgesics are recommended for the symptomatic treatment of pain. 

The authors recommend a multidisciplinary approach to skeletal-related events and often radiation therapy, surgical intervention and pharmacologic management is needed.  They find that bisphosphonates, including Zoledronic acid and Pamidronate are key in the treatment and prevention of these events by targeting the increase in osteoclastic bone breakdown by tumors.  Corticosteroids are used in the management of neurologic symptoms of spinal cord compression, although they should not be routinely used in all patients.  Opioid and nonopioid analgesics should be used if patients continue to have pain despite treatment with bisphosphonate therapy. 

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T1 Radiculopathy: Electrodiagnostic Evaluation
Jeffrey Radecki, M.D., Joseph H. Feinberg, M.D., MS, Zachary R. Zimmer, BA
HSS Journal, volume 5, #1, February 2009, 73-77

Electromyography (EMG) studies are useful in the anatomical localization of nerve injuries and in most cases, isolated lesions of a single nerve root level.  Their utility is important in identifying specific nerve-root-level injuries where surgical or interventional procedures may be warranted.  In this case report, an individual presented with right upper extremity radicular symptoms consistent with a clinical diagnosis of cervical radiculopathy.  EMG studies revealed a lesion could be more specifically isolated at the T1 nerve root and furthermore provided evidence that the abductor pollicis brevis receives predominantly T1 innervation. 

They reported upon a 63-year-old male with a six-week history of right-sided neck/arm pain and numbness after hauling heavy loads.  At the time of injury he reported progressive aching to the right periscapular region followed by radiating pain and numbness down the medial side of the right upper extremity. Paresthesias were noted predominantly in the right fourth and fifth digits with subjective complaints of loss of dexterity in the right hand manifesting as occasionally dropping objects and deterioration of penmanship. 

Spurling’s maneuver to the right reproduced concordant pain with exacerbation of radicular symptoms down the right upper extremity.  Strength examination reveals 4/5 strength on right thumb abduction and 5/5 strength in all other muscles of both upper extremities.  Sensation examination was diminished over the medial aspect of the right arm extending into the medial hand.  Reflexes were present and symmetrical in bilateral biceps, brachioradialis and triceps.  Phalen’s maneuver and Tinel signs were negative.  There were no myelopathic signs on examination. 

Nerve conduction studies were normal, this would indicate that there was relative continuity of sensory neurones originating in the dorsal root ganglion distal to the hand at the point of the recording electrodes.  This then indicated that the lesion would be most likely pre-ganglionic.  Motor nerve studies revealed mildly prolonged distal onset latency and severely reduced amplitude of the right median motor nerve.  This pointed to an underlying axonal loss which may have occurred anywhere between the anterior horn cells within the spinal cord to the distal recording motor site.  The degree of axonal loss could explain the mildly prolonged median motor distal latency due to the unreliable determination of accurate onset or alternatively it may have been secondary to a mild clinical insignificant median motor neuropathy at the wrist consistent with carpal tunnel syndrome. 

The muscle tested in this median motor exam was the abductor pollicis brevis with reported C8-T1 nerve root innervation.  However, the normal sensory conduction study suggested the site of injury was between the anterior horn and the dorsal root ganglion. 

EMG needle examination revealed abnormal spontaneous activity in the form of positive sharp waves and fibrillation in the C8-T1 innervated muscles.  The right abductor pollicis brevis revealed the most noted abnormal change in the form of severe spontaneous activity, discreet recruitment pattern and decreased recruitment interval.  The right first dorsal interosseus, flexor carpi  ulnaris and abductor digiti minimi muscles revealed mild abnormal spontaneous activity and normal recruitment pattern.  Results are mild abnormal spontaneous activity at the right lower cervical paraspinal muscles. 

All remaining muscles innervated by cervical nerve roots cranial to C8 showed no abnormal spontaneous activity, normal motor unit configuration and normal motor unit recruitment.  These electrodiagnostic studies are consistent with a severe right C8 but more likely T1 radiculopathy predominantly involving the anterior ramus division. 

An MRI revealed a right posterolateral and foraminal disc extrusion 4 mm in AP length at the T1-T2 intervertebral level.  In addition, there was no significant pathology related to the C8 nerve root at the C7-T1 disc level.  There was a mild disc bulge at C7-T1. 

The T1-T2 intervertebral disc protrusion was found to be causing significant right T1 radiculopathy. 

The patient chose to undergo conservative treatment and was subsequently referred to physical therapy for postural exercises and retraining, manual chin retractions, anterior chest wall stretching, shoulder retractions and soft tissue massage to improve segmental motion. 

The authors note that thoracic disc herniation is a rare condition that occurs in only about 1% of all disc herniations.  When they do occur, they are typically found in older patients and are predominantly found in the lower thoracic spine.  The authors further note that thoracic disc disease and diabetes mellitus represent two of the most frequent etiologies for the development of thoracic radiculopathy.  Degeneration is favorite as a prevailing process for thoracic disc herniation and the lower thoracic segments are most at risk because of the increased motion present at these levels.  When thoracic disc herniations do occur, they occur either in a posterior-central or posterior lateral direction.  At the upper thoracic levels one reason for more lateral disc herniation may be the absence of Luschka joints beginning at the C7-T1 level.  The authors noted that the electrophysiologic findings in this case help purport the more accepted claim that the abductor pollicis brevis is the only muscle in the upper extremity with chiefly a T1 inner

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Prevalence of Self-Reported Physically
Active Adults United States 2007
MMWR 2008; 57:1297-1300
JAMA March 4, 2009, volume 301, #9

This paper came from the Centers for Disease Control and Prevention and published in their Morbidity and Mortality weekly report.  The guidelines for 2008 physical activity were released in October by the US Department of Health and Human Services, and which provided new guidelines for aerobic physical activity.  This is defined activity that increases breathing and heart rate, and muscle strengthening physical activity. 

The minimum recommended aerobic physical activities by the CDC, required to produce substantial health benefits in adults is 150 minutes of moderate intensity activity per week or 75 minutes of vigorous intensity activity per week or an equivalent combination of moderate and vigorous intensity physical activity.  Recommendations for aerobic physical activity in the 2008 guidelines different from those used in healthy people 2010 (HP 2010) objectives, which calls  for adults who engage in at least 30 minutes of moderate intensity activity, five days per week or 20 minutes of vigorous intensity activity three days per week.  The analysis of their extensive survey revealed that overall 64.5% of respondents to their 2007 survey reported meeting the 2008 guidelines and 48.8% of the same respondents reported meeting HP 2010 objectives.  Public health officials should be aware that when applied to BRFSS beta, the two sets of recommendations yield different results.  Additional efforts are needed to further increase physical activity. 

They note that BRFSS is a state based random digit dial telephone survey of the noninstitutionalized US civil population aged 18 or over. 

Utilizing the 2008 guidelines, 64.5% of US adults were classified as physically active in 2007, including 68.9% of men and 60.4% of women.  They found that of the population age 65 or over, 51.2% met the minimum physical activity level and of the 18 to 24-year-old group, 74% did. 

They noted that among the racial/ethnic populations, prevalence was lower for non-Hispanic Blacks, (56.5%) then for Hispanic Whites (67.5%).  By educational level, prevalence was lower for persons who was less than a high school diploma (52.2%) and highest among college graduates (70.3%).  By US census region, prevalence was lowest among respondents in the south (62.3%) and highest among those in the west (67.8%).  A smaller percentage of persons classified as obese (57.1%) were physically active then persons classified as overweight (67.3%) or of normal weight (68.8%). 

The CDC editors found that the findings in this report indicated that 64.5% of the United States adults reported meeting the minimum level of aerobic physical activities in the 2008 guidelines using the BRFSS 2007 data.  They found that approximately one-third of US adults did not meet minimum levels of aerobic physical activity as defined in the 2008 guidelines. 

They authors concluded that extensive health benefits can be attained by engaging in physical activities beyond these levels.  They provided guidelines for people to get involved in increased physical activity. 

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Brachial Plexus Avulsion causing
Brown-Sequard Syndrome
Nordin and Sinisi
Journal of Bone and Joint Surgery, volume 91-B, #1, January 2009, 88-90

The authors note the statistics that the Brown-Sequard Syndrome occurs between 2 and 5% of patients who sustain pre-ganglionic avulsion injuries to the brachial plexus.  They classify pre-ganglionic lesions of the brachial plexus into two groups.  The first involves either the roots being ruptured in their intradural course, leaving central stumps of variable length, peripheral intradural pre-ganglionic rupture, where they are torn directly from the cord and central nervous tissue is attached to the avulsed root leaving a defect in the cord (central pre-ganglionic avulsion).  Both lead to the death of motor neurones in the anterior horn, but central avulsion is an injury to the central nervous system, it results in scarring within the spinal cord.

The authors further state that a true central avulsion causes a partial Brown-Sequard Syndrome at the time of injury and is estimated to occur in between 2 and 5% of patients with brachial plexus injuries.  They reported a case in which there was no vascular injury and no evidence of an ischemic lesion of the cord and that the deepening partial Brown-Sequard Syndrome was caused by progressive tethering and distortion of the cord by scar tissue.  They presented a second case in which there was a sudden onset of new symptoms in a patient but no signs of Brown-Sequard Syndrome at the time of injury.  They also noted that in this case the symptoms were not present at all times.  The authors stated that if there are deposits of hemosiderin, that they would attribute these findings from ischemic injury. 

They presented a third case with the early onset of these symptoms from the cord, which were directly attributable to avulsion of the spinal roots. 

The authors again note that these types of injuries can affect the sense of fine touch, vibration, proprioception, and temperature in the lower limbs.  They further state that the late onset of pain or weakness in the lower limbs, in patients who have sustained significant brachial plexus injury calls for prompt and thorough investigation to exclude a new lesion of the cervical spinal cord.

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Baseline Radiographs Not Predictive of Spondylolisthesis Surgical Outcomes
Orthopedics Today, volume 29, #2, February 2009, page 60
Abstract of North American Spine Society Presentation,
23rd Annual Meeting, Presented by Adam M. Pearson, M.D.

The author presented a multicenter spine patient outcome research trial.  The authors determine the differences between pre and postoperative levels in three key areas, through two years postoperative, correlating them with baseline radiographs.  They study degree of listhesis, disc height where low height was 5 mm or less or about one-third of normal height, and intervertebral mobility with hypermobility defined as over 10 degree rotation or 4 mm translation. 

Their primary outcome measures were SF-36 scores for bodily pain and function at Oswestry disability index scores.  Secondary measures consisted of the stenosis bothersome index and low back pain bothersome index. 

They stated that 86 of these patients had a grade I spondylolisthesis, 14% had grade II slips and 22% had low disc height.  Spine hypermobility was diagnosed in 27% of patients but the remainder had stable spines. 

They stated that their grade I group improved more of a nonoperative treatment than the grade II group.  This resulted in a greater treatment of effect at one year but these differences were no longer significant at two years.  They stated that disc height was not generally associated with outcomes.  One exception to that finding was that those patients with normal disc height showed more improvement on the spinal stenosis bothersome index one year after surgery versus those with low disc height. 

The authors also observed that hypermobile patients improved more with nonoperative treatments than stable patients.  Hypermobility should not be a contraindication to nonoperative treatment according to Pearson.  He indicated his surprise to see that more men had intervertebral hypermobility.  Most hypermobile patients were treated with instrumented fusion which suggests surgeons actually took the flexion extension x-rays into account in making their decision. 

Again the conclusion was that hypermobility should not be a contraindication to nonoperative treatment.  This was a main theme presented by Dr. Pearson. 

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Heavy Loaded School Backpacks Could Lead to Lumbar Spine Asymmetry During Loading
Orthopedics Today, February 2009, page 63

The authors presented an abstract of a paper by Timothy Neushwander, M.D., a study utilizing MRI to assess how lumbar disc height is affected when young subjects wear heavy backpacks, and which found that caudal intervertebral discs compressed the most relatively typical school backpack loads.  Lumbar symmetry was a new and unexpected finding in this study.  They studied three boys and five girls whose mean age is 11 years and had normal Cobb angles when not wearing backpacks, but these angles increased almost 10 degrees when they wore backpacks weighing 8 kg.  The hypothesis was that typical school backpack loads would significantly decrease lumbar disc height and increase lumbar curvature.  This paper was presented at the North American Spine Society 23rd Annual Meeting. 

They reported that lumbar disc height in each child using midline sagittal T2 images measured the height of their discs from L1-S1 in the supine and upright loaded states, as well as when they were loaded with 4 kg, 8kg and 12 kg backpacks.  Researchers define disc height as the average of a disc’s posterior and anterior height, and spinal compressibility as spine disc height minus post loaded disc height in millimeters with loaded discs represented by negative numbers. 

The noted that MRIs were also used to assess lumbar spine asymmetry via Cobb angles measured before and after loading.  They found that the greater the backpack load the greater the suppressed disc heights were at all levels from T12-L1 to L5-S1.  They found that L5-S1 disc was more compressible to about 1 mm of compressibility.  When you add increasing backpack loads all the way up to 12 kg you get anywhere from 1 mm compressibility and more cephalad discs to approximately 2.25 mm of compressibility. 

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Management of Symptomatic Lumbar Degenerative Disc Disease
 Madigan Vaccaro et al.

Symptomatic lumbar degenerative disc disease or discogenic back is difficulty to treat.  Patients often report transverse low back pain that radiates into the sacroiliac joints.  Radicular or claudicatory symptoms are generally absent unless there is concomitant nerve compression.  Physical examination findings are often unremarkable.  Radiographic examination may reveal disc space narrowing, endplate sclerosis, or vacuum phenomenon in the disc; magnetic resonance imaging is useful for revealing hydration of the disc, annular bulging or lumbar end-plate (Modic) changes in the adjacent vertebral bodies. The use of discography as a confirmatory study remains controversial.  Recent prospective, randomized trials and meta-analyses of the literature have helped to expand what is known about degenerative disc disease.  In most patients with low back pain, symptoms resolve without surgical intervention; physical therapy and nonsteroidal anti-inflammatory drugs are the cornerstones of nonsurgical treatment.  Intradiscal electrothermal treatment has not been shown to be effective, and arthrodesis remains controversial for the treatment of discogenic back pain.  Nucleus replacement and motion sparing technology are too new to have demonstrated long-term data regarding their efficacy. 
(J Am Acad Orthop Surg 2009; 17:102-111).
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How Do Prominent Payers View Chronic Back Pain
The Back Letter Volume 23 #9
September 2008

The centers for Medicare and Medicaid services have more impact on spinal medicine than many of the studies and systematic reviews published in elite medical journals. The CMS have expressed their views on the multifactorial nature of chronic back pain; the difficulty determining the precise cause of pain; the inadequate evidence base for many spine treatments; and the apparently lack of progress in health outcomes related to spinal complaints in the United States.  The CMS analysts are obviously voracious readers of the spinal literature.  An excerpt from a recent CMS decision stated that in general, the social and economic impact of chronic pain is enormous.  Despite rapidly increasing medical expenditures from 1997 to 2005, there was no improvement over this period in self-assessed health status, functional disability, work limitations or social functioning among respondents with spine problems.  (Martin, Deyo et al, 2008).  The growing list of treatment approaches offered as solutions for chronic low back has created confusion and frustration for patients as well as clinicians and the third party payers responsible for providing access to care (Haldeman, Dagenais 2008).  Identifying the cause for nonspecific low back symptoms remains challenging.  Haldeman stated, “We do not know the origin of low back pain in the majority of cases” and Dr. Haldeman has attributed this problem to the unique anatomic complexity of the spine.  (Haldenman 1999). 

Weiner, Kim et al 2006, reported causative underlying pathology is difficult to determine because low back, a complex clinical syndrome, derives from a multitude of causes, such as mechanical and non-mechanical factors and visceral disease.  Neurophysiologic mechanisms of pain sensation are poorly understood, adding to the difficulty in localizing the pain source.  Nachemson related the complexity of back pain not only to local pathology but also to biochemistry, pain physiology, brain science, psychology, sociology, and economics (Schoene 2007). 

Frequently, persistent low back pain is attributed to a damaged intervertebral disc, which bear some of the highest loads in the human body and is almost avascular (Huang, Sandhu 2004).  Disc damage, or degeneration, can occur as an ongoing process where ultimately the disc repaired capacity is overwhelmed leading to continued changes.  Huang and Sandhu stated, “It is not surprising that degenerative disc disease is a common phenomenon.

While from a simple mechanical aspect, it would be hypothesized that degenerative disc disease was a cause of pain, disc degeneration is also observed in individuals without pain (Boden, Davis et al 1990). 

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Can Exercise – Only,
Protocol – Driven Spinal Care Be Affective
As Standard Physical Therapy?
Ted Dreisinger, Ph. D and Vert Mooney, M.D.

The authors performed a retrospective cohort study in 307 patients with primarily chronic spinal pain disorders who are under care at two outpatient centers, a standard physical therapy clinic and an exercise only clinic.  The majority of physical therapy patients were Workers Compensation, while all of the exercise – only patients were private insurance with co-payments at each visit.  At both centers, treatment consisted of isolated strengthening exercise with equipment for the spinal musculature and other major muscles.  The standard exercise protocol focused on dynamic progressive resistance exercise with gradual and measurable loading and was typically administered two times per week for up to 12 weeks.  Patients in physical therapy also received physical modalities such as manual, thermal and electrical therapies two to three times per week.  Exercise-only treatment was carried out by exercise science staff, while physical therapy was directed by physical therapists. 

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Facet Joint Arthritis:
No Relationship to Low Back Pain
The Back Letter volume 24, #1
January 2009

The authors state that blaming radiographic facet joint arthritis as a cause of low back pain has been a fairly common clinical practice, off and on since the early 20th Century.  However, no form of imaging has proved to be capable of identifying painful facets.  It remains a matter of bitter controversy whether other diagnostic methods particularly facet joint blocks can identify pain syndromes related to these lumbar joints.  They quoted a study by Kalichman and Hunter, 2007, describing the important anatomic functions of facet joint.  A facet joint plays an important role in low transmission, they provide a posterior load-bearing helper, stabilizing the motion segment in flexion and extension and also restricting axial rotations.  They stated that the lumbar facets could conceivably cause low back pain, however, as the capsule of the facet joint, subchondral bone, and synovium are richly innervated and can be a potential source of low back pain.  They stated that the best method of evaluating potential pathologic changes in facet joints appears to be the CT scan. 

They stated that Kalichman et al found abundant facet joint changes with a prevalence of osteoarthritis rising steadily with age.  They stated that the highest prevalence of osteoarthritis was found at L4-5 followed by L5-S1, L3-4 and L2-3.  They observed that women demonstrated a higher prevalence of osteoarthritis compared with men at the L4-5 and L5-S1 levels though the difference was only statistical significance at the L4-5 level.  However, the researchers found no relationship between facet joint osteoarthritis and low back pain at any spinal level.  They stated that few studies have found predictable relationships between pain and common degenerative changes in the lumbar spine.  The spine changes continuously throughout life and few of the routine changes labeled as degenerative have a predictable relationship with pain.  They stated that a healthcare provider gazing thoughtfully at an imaging scan might want to withhold comment on facet joint osteoarthritis as well as any other common degenerative changes.