Ovid Primary Care Medicine: Office Evaluation and Management of the Adult Patient PDF
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University of Michigan Health System
2021
Goroll, Allan H.; Mulley, Albert G.
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Summary
This medical textbook, "Primary Care Medicine: Office Evaluation and Management of the Adult Patient", 8th Edition, details the approach to diagnosing and managing back pain in adult patients. It covers the pathophysiology, clinical presentation, and management of various back pain conditions.
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11/23/23, 11:09 PM Ovid: Primary Care Medicine: Office Evaluation and Management of the Adult Patient Editors: Goroll, Allan H.; Mulley, Albert G. Title: Primary Care Medicine: Office Evaluation and Management of the Adult Patient, 8th Edition Copyright ©2021 Lippincott Williams & Wilkins > Table...
11/23/23, 11:09 PM Ovid: Primary Care Medicine: Office Evaluation and Management of the Adult Patient Editors: Goroll, Allan H.; Mulley, Albert G. Title: Primary Care Medicine: Office Evaluation and Management of the Adult Patient, 8th Edition Copyright ©2021 Lippincott Williams & Wilkins > Table of Contents > Section X - Musculoskeletal Problems > Chapter 147 - Approach to the Patient with Back Pain Chapter 147 Approach to the Patient with Back Pain Back pain is the second most frequent complaint in primary care practice and one of the leading causes of disability. Most back pain is caused by musculoligamentous strain, degenerative disk disease, or facet arthritis and responds to symptomatic treatment. Disk disease is often responsible for recurring mild discomfort of the low back and episodes of severe back pain with sciatica. Occasionally, back pain may result from problems originating outside of the spinal axis. Serious underlying problems such as tumor, infection, or vertebral compression fracture must be kept in mind. The prevalence of back pain and the disability it causes requires that the primary physician be skilled in its assessment and conservative management and knowledgeable about commonly sought complementary therapies as well as the risks and benefits of interventional measures. Even after consulting specialists, many patients will seek review of options and recommendations with their primary care physician. PATHOPHYSIOLOGY AND CLINICAL PRESENTATION (1,2,3,4,5,6,7,8,9,10) Musculoligamentous Strain Muscle fibers or distal ligamentous attachments of the paraspinal muscles may tear, usually at the iliac crest or lower lumbar/upper sacral region. Resultant bleeding and spasm cause local swelling and marked tenderness at the site of injury. The patient typically presents after a specific episode of bending, twisting, or lifting. The strain is usually severe and is associated with a feeling of something giving way in the lower back. The onset of pain in the lower lumbar area is immediate. Pain radiates across the low back, often to the buttock and upper thigh posteriorly. Radiation of pain into the lower leg is rare because usually no injury to the nerve roots has occurred. Lumbar Disk Disease The normal disk consists of a gelatinous nucleus pulposus surrounded by a fibrous annulus and serves to provide shock absorption and flexibility. The pathophysiology of disk disease remains incompletely understood but involves degenerative and attritional changes in the lower lumbar disks caused in part by the concentration of force at the lumbosacral level, especially between the L4 and S1 levels. These stresses result from the enormous longitudinal and shear forces associated with upright posture, aggravated by bending strain. A wide variety of changes in disk positioning result as consequences of these stresses, ranging from bulging to frank herniation. A consistent terminology for disk configuration has been recommended and implemented by the radiology community for use in their imaging reports. “Bulging” connotes a circumferential spreading out of the disk without any tear or deformity of the disk annulus; it is not considered herniation. “Herniation” refers to changes with greater potential to cause difficulty. Herniation is designated as “protruding” if there is a focal asymmetric extension (usually posterolateral) of the annulus and nucleus beyond the interspace. If there is a rent in the annulus but the nucleus remains in one piece even though it has extended well beyond the interspace, the herniation is designated as “extruding.” Disk herniation is labeled as “sequestering” if a piece of the nucleus has broken off and lies in the spinal canal or elsewhere. One will find these terms used in descriptions of disk anatomy on CT and MRI scanning. It is believed that pain ensues as a consequence of inflammation triggered by nerve contact with the herniated nucleus pulposus. Disk herniation that compresses and irritates a lower lumbar or upper sacral nerve root may result in radicular symptoms, sometimes referred to generically as “sciatica” (although the proper use of the term should be reserved for radicular pain in the distribution of the sciatic nerve, which encompasses the roots of the L4, L5, S1, and S2 nerves joining in the lumbosacral plexus and leaving the pelvis as the sciatic nerve). Radicular pain is the symptomatic hallmark of nerve root irritation. Disk protrusion or extrusion is present in 95% of cases, although it is also present in many asymptomatic persons. Radicular pain presents as a sharp or burning sensation radiating down the posterior or lateral aspect of the leg to the ankle or foot (depending on the specific nerve root involved). The pain may be worsened by cough, Valsalva maneuver, or sneezing, and may be accompanied by paresthesias, numbness, and weakness in the areas supplied by the involved nerve root (Fig. 147-1). Recurring attacks of localized back pain also occur, believed mediated by pain receptors in the longitudinal ligaments stimulated by the herniated disk, and most pronounced with prolonged sitting, which places extra weight-bearing stress on spinal structures. More than 95% of disk protrusions and extrusions occur at L4 to L5 or L5 to S1, with the L5 and S1 nerve roots the most often affected, followed by L4. With lower lumbar disk disease, especially disk extrusion, lumbar paraspinal muscle spasm often occurs and limits lumbar motions. A listing away from the side of the disk extrusion—so-called sciatic scoliosis—may develop, along with tenderness of the lower lumbar spine and sciatic notch. The natural history and clinical course of degenerative lumbar disk disease often begin with a several-year history of recurring mild mid-low back pain related to minor back strain +/- facet-joint arthritis, with symptoms usually clearing spontaneously within a few days. Attacks typically increase in frequency and severity at intervals of several months to several years. Finally, an episode of persistent pain accompanied by radicular symptoms develops, often triggered by a seemingly trivial stress (e.g., twisting or bending over in the shower to pick up the soap). Fortunately, the clinical course is quite favorable for most patients, with significant improvement or resolution by 6 weeks, even in the setting of mild numbness or weakness. A minority, who typically present with very severe symptoms and marked neurologic deficits, fail to improve by 6 weeks and risk a more sustained clinical course, but even they may experience considerable improvement with time. Spinal Stenosis This often-overlooked etiology is becoming better appreciated as an important cause of chronic low back and lower extremity complaints. It occurs predominantly in elderly individuals with osteoarthritic spurring, chronic disk degeneration, and facet joint arthritis. Spinal stenosis is also found in young people who have a congenitally narrowed lumbar spinal canal. In either case, the changes narrow the canal and the neuroforamina, leading to root impingement and pain. P.1234 https://ovidsp.dc1.ovid.com/ovid-new-a/ovidweb.cgi 1/18 11/23/23, 11:09 PM Ovid: Primary Care Medicine: Office Evaluation and Management of the Adult Patient FIGURE 147-1 Dermatomes of the lower extremity. (Reprinted with permission from Norris TL, Lalchandani R. Porth's Pathophysiology, 10th ed. Philadelphia, PA: Wolters Kluwer, 2018.) P.1235 The characteristic symptom is pain that is worsened by standing, walking, or other activities that cause spinal extension and is relieved by rest, especially by sitting, or lying down and flexing the spine and hips. Patients report pain in the low back, gluteal region, or lower extremities if there is nerve root impingement; often, it is bilateral. Numbness or weakness in a radicular pattern may accompany the pain in the legs. Because symptoms are often worsened by walking and relieved by sitting down and resting, they can mimic vascular insufficiency and are sometimes referred to as “pseudoclaudication” or “neuroclaudication.” On examination, the spine demonstrates good range of motion and little focal tenderness. Minor neurologic deficits (e.g., a diminished ankle jerk) may be present, but no pattern is characteristic. The natural history of the condition is generally favorable, with only 15% of patients reporting clinical worsening over 5 years; 70% stay the same and 10% improve. Cauda equina syndrome is very rare in spinal stenosis. Spondylolisthesis The term denotes forward subluxation of a vertebral body. In adults, the condition results from degenerative changes and arthritis of the facet joints, usually at L4 to L5 or L5 to S1, with forward slippage of 10% to 20% of the diameter of the vertebral body. About 70% of patients with spondylolisthesis have chronic low back pain; sciatica is infrequent. The pain is caused by strain imposed on the ligaments and intervertebral joints. Ankylosing Spondylitis and Other Spondyloarthropathies The seronegative spondyloarthropathies (which include ankylosing spondylitis, psoriatic arthritis, reactive arthritis, and arthritis associated with inflammatory bowel disease) have both peripheral and axial skeleton manifestations. There is considerable overlap among these inflammatory joint diseases, which share involvement of the sacroiliac joints and axial skeleton, limb joints, and entheses (sites of insertion of ligaments and tendons [e.g., Achilles, patellar, plantar fascia] into bone), as well as nonarticular sites (e.g., uveal tract, skin, bowel, and aortic valve). Focal tenderness may be reported at sites of involvement. A relation to mechanical stress has been invoked to explain the distribution of findings. There is a strong association with HLA-B27 positivity, suggesting an immune pathophysiology; rheumatoid factor is negative. Male predominance is the rule. Ankylosing spondylitis is the most common of these conditions. Its characteristic features helpful for diagnosis include low back pain of at least 3 months' duration, improvement with exercise but not with rest, limitation of lumbar spine motion and chest expansion, and bilateral sacroiliitis or severe unilateral disease. Spinal involvement is most prominent in young men; onset is gradual. Morning spinal stiffness is typical. Spinal radiographic findings are often unremarkable in the early phases, but films of the sacroiliac joints may show narrowing of the joint space and reactive sclerosis (“sacroiliitis”). Eventually, the sacroiliac joint space becomes obliterated, and fusion follows. Squaring of the vertebral bodies is the first spinal radiologic manifestation, followed by the development of syndesmophytes. Similar although less florid changes may occur in the other seronegative spondyloarthropathies. https://ovidsp.dc1.ovid.com/ovid-new-a/ovidweb.cgi 2/18 11/23/23, 11:09 PM Ovid: Primary Care Medicine: Office Evaluation and Management of the Adult Patient Vertebral Compression Fracture In normal bone, this fracture requires severe flexion-compression force. It is acutely painful. Spontaneous vertebral body collapse, or pathologic fracture, is most commonly seen in elderly persons with severe osteoporosis (see Chapter 164), in patients taking long-term glucocorticoids (see Chapter 105), and in cancer patients with lytic bony metastases. Usually, the history is one of sudden back pain brought on by a minor stress. The discomfort is noted at the level of fracture, with local radiation across the back and around the trunk, but rarely into the lower extremities. The fracture is more likely to occur in the middle or lower levels of the dorsal spine, which helps to differentiate the problem from lumbar disk herniations, 95% of which occur at the level of the L4 or L5 disk. Neoplasms The most common spinal tumor is metastatic carcinoma. Breast, lung, prostate, gastrointestinal, and genitourinary neoplasms commonly metastasize to the spine. Purely lytic lesions, which are often caused by renal or thyroid carcinoma, are seen occasionally. Myeloma is the most common primary bone tumor involving the spine. About 80% of patients are older than 50 years of age. Typically, metastasis is hematogenous to the marrow of the vertebral bodies. Involvement of the periosteum and bony destruction lead to pain, and extension to the spinal cord can produce neurologic deficits. The disk spaces are usually spared, and disk space height is maintained, helping to differentiate the condition from degenerative disease. Collapse of the vertebral body as a result of bony destruction may be difficult to differentiate from compression fracture if osteoporosis is present. Extension into the epidural space or vertebral body collapse can lead to spinal cord compression; vascular compromise by the tumor may also contribute to cord injury. Although only 30% of persons with metastatic disease as the cause of back pain give a history of previous cancer, in those that do, the probability of spinal metastasis is high. Approximately 90% report night pain and pain unrelieved or worsened by lying down or bed rest. A history of prior malignancy, insidious increase in pain in a region atypical for disk disease (e.g., the midback), and failure to obtain relief by lying down are highly predictive of metastatic tumor. The clinical presentation is one of insidious onset of back pain, gradually increasing in severity and aggravated by activity and lying down. Location can be anywhere in the spine, but occurrence in an area atypical for degenerative disk disease (e.g., the midback) is suggestive. The worsening with activity, lack of relief on lying down, and atypical location in conjunction with focal spinous tenderness should raise suspicion for bony metastasis. Extension into the epidural space is heralded by increasing back pain followed by neurologic symptoms a few weeks to months later. Besides back pain, manifestations of epidural invasion include upper motor neuron signs (proximal muscle weakness, hyperreflexia, upgoing toes) sensory loss in a dermatomal distribution, and autonomic dysfunction (urinary retention, fecal incontinence). Prognosis is poor without early intervention. Intraspinal tumors may present in the same manner as herniated disks. However, marked progression of neurologic deficits despite adequate conservative therapy is a clue to the existence of a tumor inside the spinal canal. Extraspinal tumors may eventually cause root impingement and simulate discogenic sciatica. Tumors of the retroperitoneum, pelvis, and large bowel may extend to the roots. This is a very late development; metastases may occur earlier. Infection Back pain resulting from infection is rare but important to detect. An identifiable source is found in 40% of cases; possibilities include urinary tract infection, skin abscess, indwelling catheter, and intravenous drug abuse. Vertebral osteomyelitis is P.1236 usually hematogenous in origin but may occasionally result from a spinal procedure, such as lumbar puncture, myelography, discography, or disk surgery. In addition to involving the vertebral bodies, it may extend into the disk space, producing a very painful discitis. In the absence of discitis, the presentation is typically one of dull, continuous back pain, often in conjunction with low-grade fever and spasm over the paraspinous muscles. Tenderness to percussion over the involved vertebrae is common, but fever and elevated white cell count are absent in up to half of cases. A compression fracture or an epidural abscess may ensue. Staphylococcus aureus accounts for about 60% of bacterial cases and enterobacteria for 30%. Epidural abscess develops in the context of bacteremia or osteomyelitis. The infection presents as back pain, focal tenderness, and fever. Fever and spinal tenderness are present in about 85% of cases. If the condition is not promptly treated, it may extend to compromise the local blood supply to the spinal cord and rapidly progress from spinal ache to major motor and sensory deficits within hours to a few days. Psychogenic Disease Patients with depression may present complaining of chronic low back pain. Often, they have a history of previous back problems or onset at the time of a minor injury, with the depression amplifying the presentation and prolonging the clinical course. Mild muscle spasm may be noted on physical examination. Characteristically, the intensity of the symptoms and the degree of disability are much greater than the minor limitations found on examination would suggest. Multiple somatic symptoms are common (see Chapter 227). Other patients may have an underlying somatization disorder. Many of these patients appear refractory to therapy and are often unwilling to take an active role in their treatment. Some even seem to derive a sense of legitimacy and self-worth from their suffering (see Chapter 230). Malingering implies conscious deception for the sake of obtaining gain from being ill. Inconsistencies among symptoms and physical findings typify malingering, which can be brought out by distracting the patient during the physical examination. Cauda Equina Syndrome Although the spinal cord ends at the L1 level, the collection of nerve roots that make up the cauda equina is subject to injury by any process that compromises the spinal canal below the L1 level. Massive midline disk herniation is the most common cause of cauda compression and a serious, although very infrequent, event that requires prompt attention. In contrast to the clinical presentation of simple root impingement, the presentation in cauda equina syndrome includes urinary retention in almost 90% of cases. Another characteristic feature is saddle anesthesia (a reduction in sensation over the buttocks, upper posterior thighs, and perineum), which is reported by about 75% of patients. Both of these clinical findings are a consequence of sacral root compression, as is a decrease in anal sphincter tone, which is noted in about two thirds of cases. Sciatica and lower extremity motor and sensory deficits are prominent and often bilateral. Patients may report falling. Piriformis Syndrome This cause of sciatic nerve pain derives from compression of the sciatic nerve where it is overlaid by the piriformis muscle. Any condition that causes swelling or injury to the piriformis muscle (running, stretching, lunging) may also trigger the complaint, which is one of focal pain in the midbuttock and the finding of tenderness in the sciatic notch. Symptoms are typically worse with sitting and with external rotation of the hip. Other presumed causes range from external compression by a thick wallet or tool placed in one's back pocket to prolonged sitting on hard surfaces. DIFFERENTIAL DIAGNOSIS (4) The differential diagnosis of back pain can be considered in terms of underlying pathophysiology (Table 147-1). Of note, the vast majority of cases (97%) are mechanical in origin, with less than 1% due to infection, neoplasia, or inflammatory disease of the spine; about 2% represent referred pain from visceral disease due to aortic, pelvic, renal, or gastrointestinal sources. WORKUP (1,2,4,5,7,8,9,11,12,13,14,15,16,17,18) Even with the advent of sophisticated spinal imaging techniques, the history and the physical examination remain critical to the effective evaluation and management of back pain. The findings elicited are often diagnostic, and even if they are not, they can help to guide test selection and ensure timely referral. Overreliance on imaging studies often results in false-positive diagnoses. History In elucidating the basic features of back pain (i.e., quality, location, onset, radiation), one should also inquire specifically into symptoms that are potentially indicative of serious underlying disease (e.g., fever, progressive neurologic deficits, bilateral deficits, bladder dysfunction, saddle anesthesia, persistent pain unresponsive to bed rest or worsened by https://ovidsp.dc1.ovid.com/ovid-new-a/ovidweb.cgi 3/18 11/23/23, 11:09 PM Ovid: Primary Care Medicine: Office Evaluation and Management of the Adult Patient lying down). A history of recent injury and a prior history of cancer are other critical elements to be noted, as are previous therapy for back problems, recent lumbar puncture, concurrent infection, and prolonged use of high-dose corticosteroids. The presence of sciatica helps to narrow the differential diagnosis (see Table 147-1). Aggravating and alleviating factors may have important diagnostic significance. Morning stiffness in the back that is relieved by activity suggests ankylosing spondylitis or other inflammatory conditions. Worsening or onset of symptoms P.1237 with standing or walking and relief with bending or sitting is characteristic of spinal stenosis, whereas worsening with sitting, driving, or lifting points to lumbar disk herniation. Malignancy is suggested by pain in a location atypical for degenerative disease (e.g., the midback), as well as by pain in any location that is worsened not only with activity but also on lying supine. TABLE 147-1 Important Causes of Low Back Pain Mechanical (97%) Nonmechanical Spinal Condition (1%) Visceral Disease (2%) Lumbar strain or sprain (70%) Neoplasia (0.7%) Aortic aneurysm Degenerative disk or facet disease (10%) Metastatic carcinoma Renal disease Herniated disk (4%) Multiple myeloma Pelvic disease Osteoporotic compression fracture (3%) Spinal cord tumor Abdominal disease Spondylolisthesis (2%) Lymphoma, leukemia Trauma (<1%) Discogenic disease Infection (0.01%) Osteomyelitis Epidural abscess Septic discitis Inflammatory disease (0.3%) Ankylosing spondylitis Psoriatic arthritis Reiter syndrome Inflammatory bowel disease Adapted from Deyo RA, Weinstein JN. Low back pain. N Engl J Med 2001;344:363, with permission. Associated symptoms are critical to check for, especially fever (raising the question of epidural abscess) and neurologic deficits (suggestive of cord or root injury). Is there any difficulty in standing or climbing stairs, urinating, or maintaining fecal continence? Is there truncal or saddle anesthesia? If so, a high index of suspicion is required for cord or cauda equina injury. Typical unilateral root symptoms (pain, numbness, weakness) in a characteristic lumbosacral root distribution suggest root impingement, but bilateral radicular symptoms, especially if severe and new in onset or rapidly progressive, should raise concern about cauda equina syndrome or epidural injury. The patient should be asked to describe the effect of the back pain on daily activities. Emotional and social stressors are sought if the severity and duration of the symptoms appear to be disproportionate to the amount of organic disease present. Under such circumstances, it is important to check for depression (see Chapter 227) and manifestations of somatization disorder (see Chapter 230). Physical Examination Before examining the back, one should check the skin, abdomen, rectum, groin, pelvis, and peripheral pulses for conditions that might mimic the symptoms of spinal disease. A classic example is an outbreak of herpes zoster, with the pain in a dermatomal distribution presaging the skin outbreak. Another is claudication due to vascular insufficiency, giving unilateral or bilateral leg pain with walking. In addition, one looks for fever, skin abscess, breast mass, pleural effusion, prostate nodule, lymphadenopathy, joint inflammation, and other signs of systemic, infectious, or malignant disease that may affect the spine. Thigh and calf circumferences are measured to detect evidence of atrophy, and joint motions of the lower extremities are tested. Back Examination The examination of the back begins with the patient standing and the back uncovered. One checks for any abnormalities in symmetry, muscle bulk, posture, and spinal curvature. Flexibility is assessed, with any muscle spasm or spinal segments that do not move freely noted. A description of what limits back motion is more important than an estimation of degrees of motion, which is imprecise at best. The spine is palpated for focal tenderness suggestive of tumor, infection, fracture, disk injury, and disk herniation. Sensitivity of the lower lumbar spine and sciatic notch is usually found with lower lumbar disk herniation. Sacroiliac tenderness to deep palpation is sometimes present in ankylosing spondylitis, but the finding is nonspecific. A finding of focal spinous process tenderness, especially in a location atypical for degenerative disease (e.g., the midback), should raise suspicion for spinal pathology due to metastatic disease or infection. If piriformis syndrome is suspected, checking for focal tenderness to deep palpation in the mid buttock and sciatic notch as well as for pain worsened by external rotation of the hip can help confirm the diagnosis. Straight Leg Raising Test (SLR) https://ovidsp.dc1.ovid.com/ovid-new-a/ovidweb.cgi 4/18 11/23/23, 11:09 PM Ovid: Primary Care Medicine: Office Evaluation and Management of the Adult Patient This diagnostic maneuver is an important component of the assessment for disk disease. It serves as a sensitive indicator of lower lumbar disk herniation, particularly in patients with sciatica. SLR testing is based on the observation that an L5 or an S1 nerve root tethered by a herniated disk causes radicular pain if stretched. In the presence of a severely herniated disk, the additional root stretching causes impingement and pain, especially with an L5 to S1 disk injury. Straight leg raising is performed in the supine position with passive lifting of the patient's leg at the heel while the knee is kept fully extended. The test is performed both on the side of the reported sciatica (ipsilateral SLR testing) and on the opposite side (contralateral or crossed SLR testing). A test result is positive if the sciatica is reproduced as the leg is elevated between 30 and 70 degrees. Reproduction of the sciatica should not be confused with hamstring muscle tightness, which can also cause discomfort on SLR, especially as elevation approaches 90 degrees. (Elevation beyond 80 degrees exerts little additional stretch on the nerve root and is not of much meaning.) If severe pain is reported on elevation and resistance occurs, yet the leg can be raised another 20 or 30 degrees when the patient is distracted, the test result is “negative” and other causes of the pain should be sought, such as hamstring muscle tightness. Dorsiflexion of the ankle at the extreme of SLR may exacerbate the pain of disk herniation on SLR testing and is particularly useful if the SLR test result is equivocal. The earlier the onset of pain during the test, the more specific is the result and the greater is the degree of disk herniation. The test sensitivity averages 80% for ipsilateral SLR; specificity is low (about 40%). The specificity of a positive contralateral SLR test result is considerably higher (75%), but the sensitivity is only 25%. A large disk herniation with an extruded fragment is an important cause of a positive contralateral SLR result. Interestingly, about 50% of persons with piriformis syndrome as the cause of sciatica pain may manifest a positive ipsilateral SLR test. Much less L4 and minimal L2 or L3 movement occurs during SLR testing, so that it is less useful to detect disk herniation above L4 to L5. Femoral nerve sensitivity is usually present with higher lumbar (L2, L3, or L4) root irritation. Flexing the knee with the patient lying in a prone position may reproduce the back and anterior thigh pain of upper lumbar disk herniation. Neurologic Examination (see Fig. 147-1) The examination is most efficiently performed by concentrating on the areas of compromise suggested by the history. The patient with sciatica is most likely to have deficits in the territory of the L5 and S1 roots and should be tested accordingly. The person with back pain radiating to the anterior thigh and associated quadriceps weakness should be tested for L4 function. A history suggestive of epidural injury requires a check for signs of upper motor neuron compromise (reduced proximal muscle strength, hyperreflexia, upgoing toes) and dermatomal sensory deficits at the level of suspected involvement. Concern about cauda equina syndrome should focus the physical examination on the detection of saddle anesthesia and bilateral motor and sensory deficits in the lower extremities. Tests for S1 root function (L5 to S1 disk) include tiptoe walking, plantar flexion against resistance, ankle deep tendon reflexes, and lateral foot sensation. A loss of plantar flexion occurs only with severe disk herniation (low sensitivity, high specificity). Tests for L5 root function (L4 to L5 disk) include heel walking (an imprecise test), dorsiflexion of the ankle and big toe against resistance, and sensation on the anterior medial dorsal foot (Fig. 147-1). For a suspected upper lumbar disk lesion (L4 root), one notes the knee deep tendon reflexes, quadriceps strength, and sensation about the medial ankle. The sensitivity of any single neurologic test for the diagnosis of lumbar disk protrusion or extrusion is no greater than 50%, but it can be enhanced to almost 90% when clusters of findings are considered. The most accurate assessment of sensory function is attained by pinprick testing, which is most efficiently performed by limiting the examination to a few key distal dermatomal areas in the feet (see Fig. 147-1) and noting any asymmetry of response. P.1238 Responses to neurologic testing and spinal examination in patients with psychological stress may appear to be neuroanatomically inappropriate, but often they are diagnostically meaningful. Disturbances in strength or sensation that do not correspond to nerve root innervation patterns, inconsistency of responses to maneuvers, overreaction to palpation or passive movement, superficial or widespread tenderness, and pain on sham testing of spinal rotation (arms kept at sides while hips are rotated) are among the characteristic responses. The presence of three or more of these responses suggests considerable psychological overlay to the patient's back pain. Laboratory Studies For the majority of patients with low back pain, a careful history and a physical examination usually suffice for diagnosis at the time of the initial office visit. The utility of imaging studies is limited to a few specific situations, many of which are also indications for referral or consultation (see later discussion). Lumbosacral Spine Imaging In most instances of patients presenting with low back pain and suspected disk disease, the routine ordering of plain lumbosacral spine films is low in yield and neither costeffective nor useful for decision making. However, when tumor, fracture, infection, or spondylolisthesis is a concern, plain films can serve as a readily available diagnostic tool. Nonetheless, early radiography of the back is indicated in some selected situations, as when the physician suspects (a) malignancy (patient >50 years of age, focal persistent bone pain unrelieved by bed rest, a history of malignancy); (b) compression fracture (prolonged corticosteroid therapy, postmenopausal woman, severe trauma, focal tenderness); (c) ankylosing spondylitis (young male patient, limited spinal motion, sacroiliac pain); (d) chronic osteomyelitis (low-grade fever, high sedimentation rate, focal tenderness); (e) major trauma; and (f) major neurologic deficits. Back pain localized to the high lumbar or thoracic region is also an indication for prompt spinal radiography because compression fracture and metastatic tumor are common in these areas. Although plain films might be helpful in these circumstances, they are not always the imaging study of choice and should not delay proceeding to more definitive imaging with magnetic resonance imaging (MRI) or computed tomography (CT) (see later discussion). For example, in early osteomyelitis, there may be no visible bony changes for at least 10 to 14 days; for spinal metastasis, the false-negative rate is 30% even in persons who present with epidural cord compression and higher in earlier stages of spinal involvement. In patients with a spondyloarthropathy, characteristic changes in SI joints may not appear until years after onset of symptoms. Computed Tomography and Magnetic Resonance Imaging Clinical suspicion of cauda equina syndrome, epidural abscess, or cancer-related epidural spinal cord compression is an indication for urgent spinal imaging by either MRI or CT. Such imaging should be obtained as quickly as possible because of the risk of severe and irreversible neurologic damage in the absence of timely intervention. CT and MRI are also indicated in persons being considered for surgical intervention to relieve persistent severe symptoms of disk herniation or other surgically amenable disease such as spinal stenosis. Both imaging modalities are very sensitive for the detection of lumbar disk disease and spinal stenosis and can provide anatomic detail of some surgical value. Besides being more costly, MRI often triggers a claustrophobic response, but no radiation exposure is involved. MRI and CT should be limited to patients who are either sufficiently symptomatic that surgical intervention must be considered or are suspected of having serious systemic disease. The high sensitivity of these tests for disk disease can produce misleading results unless the patient and clinician are aware that disk bulges and protrusions are extremely common (50% and 30%, respectively) in asymptomatic people. Magnetic resonance imaging. MRI is the test of choice in suspected cauda equina syndrome, epidural abscess, or cancer-related epidural spinal cord compression by virtue of its superiority in detecting soft tissue pathology. In most instances, it obviates the need for myelography. MRI is also the best test for detecting early osteomyelitis and is the noninvasive test of choice for spinal cord tumors, epidural abscess, and epidural cord compression due to tumor or vertebral collapse. MRI may reveal such pathologic findings earlier than CT because it can detect marrow changes, which precede bony changes. MRI sensitivity for cancer-related back pain is estimated to be 93% and sensitivity to be 97%. MRI is superior to CT for the detection of disk pathology, including the tear of a disk annulus, manifesting a high-intensity zone on T2-weighted images in the posterior aspect of the involved disk; however, the relation between the finding and pain is not well established. There is no radiation exposure, but patients have to be able to lie in the scanner for up to 45 minutes. The presence of an implantable cardiac device is usually a contraindication to MRI scanning. Rapid MRI is a variant of magnetic resonance technology that is quicker, less expensive, and slightly less sensitive than conventional MRI but is more sensitive than plain films. It has been suggested as an alternative to plain films and conventional MRI for the detection of cancer-related back pain. Decisionanalysis study finds that it is unlikely to be costeffective: It is associated with an incremental cost per quality-adjusted life year of additional survival of nearly $300,000, nearly six times the norm for a cost-effective modality. MRI with imaging under loading stress is being explored for use in evaluation of low back pain, made increasingly possible in part by the advent of more open MRI scanners. The rationale is that images taken with the patient standing and bearing weight (i.e., under stress) may provide more clinically relevant information than those taken with the patient supine. Alternatively in a conventional supine study, a vest can be placed on the supine patient with cords that pull towards the footplate, providing axial force. Critical review of existing studies finds the available evidence insufficient regarding efficacy with respect to clinically meaningful outcomes to warrant use of this approach outside the research https://ovidsp.dc1.ovid.com/ovid-new-a/ovidweb.cgi 5/18 11/23/23, 11:09 PM Ovid: Primary Care Medicine: Office Evaluation and Management of the Adult Patient setting at this time. Although such imaging is being marketed directly to consumers, they should not be encouraged to seek its use since the benefits and risks have not been adequately defined. Of note, up to 15% of patients report new or worsening pain during the procedure. Follow-up MRI scanning in persons treated for sciatica and lumbar disk herniation was not found in randomized study to be helpful in distinguishing between those who responded to treatment and those who did not. As noted, many studies have found great overlap between MRI findings in persons who are symptomatic and those who are not. Specificity is limited. Despite frequent patient requests for repeat imaging, its utility is largely limited to situations where an interventional procedure is planned on the basis of clinical findings and anatomical information is needed to help guide it, or there is new onset of important neurologic impairment or focal bone pain. Computed Tomography. CT scanning is much faster, less expensive, and more readily available than MRI, but it involves radiation exposure and is less sensitive for the detection of infection, tumor, nerve injury, and disk pathology. In addition, CT does not provide the visualization of the entire spine or upper vertebrae that MRI does (desirable features if the differential P.1239 diagnosis includes intraspinal tumor and disk herniation at an upper level). CT does provide excellent bony detail; contrastenhanced study is a reasonable alternative to MRI when the latter is contraindicated, unavailable, or impractical. It can show changes in vertebral bodies caused by tumor and infection, although not as early as MRI, which can better detect early marrow changes. Myelography Traditional myelography has been largely replaced by MRI. It has been used in conjunction with CT in patients with progressive neurologic deficits, especially those with findings suggestive of injury to the spinal cord (e.g., loss of sphincter control, bilateral numbness and weakness) who have a contraindication to MRI scanning. The temptation to perform myelography in the patient with chronic refractory pain is strong, but test use should be reserved for patients with objective findings that are amenable to surgery or radiation therapy. Risks include infection, bleeding, and iatrogenic worsening of the neurologic state; the frequency of adverse effects can approach 20%. Radionuclide Scanning The moderately high sensitivity of the technetium bone scan for osteomyelitis and metastatic disease and its wide availability make it a reasonable consideration for the patient presenting with any combination of fever, weight loss, persistent back pain, history of malignancy, concurrent infection, and markedly elevated sedimentation rate. Gallium scanning is sometimes useful in defining soft tissue involvement by infection or abscess formation. Discography This invasive diagnostic procedure is performed on patients believed to be suffering from a tear of the disk annulus. Under fluoroscopic guidance, disks are injected with contrast, which characteristically increases pain in the involved disk and helps to visualize the tear on follow-up CT scan. However, even persons without a tear might have pain on disk injection. MRI can also visualize such tears but cannot confirm the relationship between the tear and the patient's pain. Immunoelectrophoresis Serum and urine electrophoresis is helpful in cases of suspected multiple myeloma; crude screening with a complete blood cell count and determination of the erythrocyte sedimentation rate and serum globulin level is probably sufficient if clinical suspicion is not high. A diagnosis of myeloma must be suspected if back pain in an older person is accompanied by unexplained anemia and a very high sedimentation rate. However, such findings are quite nonspecific and may also be caused by a chronic inflammatory process. Electromyography Electromyography may be needed to document peripheral nerve deficits and help to select patients who require myelography. Workup for Spondyloarthritis The diagnostic criteria for the seronegative spondyloarthropathies have been revised to take advantage of earlier diagnosis made possible by MRI scanning, which can detect inflammation in the sacroiliac joints long before changes become evident on plain films. The Assessment of Spondyloarthritis International Society (ASAS) has developed revised classification criteria that incorporate MRI findings (Table 147-2). For early detection of the axial spondyloarthritis, the revised criteria show sensitivity and specificity of 82.9% and 84.4%, respectively; for peripheral spondyloarthritis, the criteria show sensitivity and specificity of 77.8% and 82.9%, respectively. TABLE 147-2 ASAS Classification Criteria for Peripheral and Axial Spondyloarthropathiesa A. Peripheral Spondyloarthritis Οnly peripheral manifestations Age <45 years at onset Arthritis or enthesitis or dactylitis plus ≥ 1 articular feature, or ≥2 other nonarticular features Articular features: arthritis, enthesitis, dactylitis, inflammatory back pain at any time in the past or family hx of spondyloarthritis Nonarticular features: uveitis, psoriasis, inflammatory bowel disease, previous infection, HLA-B27 gene, sacroiliitis on MRI or plain film B. Axial Spondyloarthritis ≥3 months of back pain Age < 45 years at onset Sacroiliitis on imaging plus ≥1 spondyloarthritis feature or HLA-B27 plus 2 other spondyloarthritis features: Sacroiliitis: active inflammation on MRI Spondyloarthritis feature: inflammatory back pain, enthesitis (heel), uveitis, psoriasis, inflammatory bowel disease, family hx, HLA-B27 positivity, elevated C-reactive protein. a Adapted from Rudwaleit M, van der Heijde D, Landewe R, et al. The Assessment of Spondyloarthritis International Society classification criteria for peripheral spondyloarthritis and for spondyloarthritis in general. Ann Rheum Dis 2011;70:25. SYMPTOMATIC MANAGEMENT (1,2,3,4,7,8,9,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51, Treating pain etiologically is always the best means of achieving symptomatic relief, but because much back pain is not directly amenable to etiologically directed therapy, it requires a host of other measures effective for pain management. Time is an important component of management for acute nonspecific low back pain, since most forms are self- https://ovidsp.dc1.ovid.com/ovid-new-a/ovidweb.cgi 6/18 11/23/23, 11:09 PM Ovid: Primary Care Medicine: Office Evaluation and Management of the Adult Patient limited. More chronic back pain poses a greater challenge, informed by advances in understanding the neurophysiology and psychology of chronic nonmalignant pain (see Chapter 236) and addressed by increasing application of nonpharmacologic measures. Radiculopathy represents a more specific form of nerve injury requiring consideration of interventional measures. Acute Nonspecific Back Pain Acute nonspecific back pain (no evidence of neurologic compromise or other serious pathology) is best managed conservatively because prognosis is generally favorable. Such pain resolves in about one third of patients by 1 week and in two thirds by 6 to 7 weeks. The reassuring effect and the overall significance of such information when delivered by the primary care clinician cannot be overemphasized—meta-analysis finds significant reductions in worry and in visits for low back pain. Impact is greatest when the information is delivered in the primary care setting. Because prognosis is favorable for the majority of persons with acute nonspecific low back pain, it is hard to demonstrate significant benefit for a specific treatment modality. Consequently, few commonly resorted-to measures are associated P.1240 with evidence of significant benefit in randomized trials. The majority of patients recover during this time regardless of measures taken. Nonetheless, patients having considerable pain will present for help, and treatment options need to be considered. FIGURE 147-2 Comfortable position for bed rest. Initial Symptomatic Relief Evidence is strongest for rest and topical heat. Acutely, heat, rest and even bed rest may be self-initiated by the patient. In a well-designed randomized study, a heat wrap shows moderate ability to improve pain and reduce disability at 5 days. There is no evidence that bed rest or generalized reduction in activity is any better than remaining active. Moreover, prolonged bed rest leads to counterproductive deconditioning (see Activity Prescription). Nonetheless, patients seek advice regarding best positions when in bed or lying down elsewhere. The most comfortable positions for bed rest and for sleep are those that reduce muscle spasm and disk-herniating/muscle tightening forces. Usually these entail either lying supine with a large pillow tucked under the knees and a small pillow folded under the head (see Fig. 147-2) or lying on one's side with the hips and knees flexed and a pillow between the knees. Lying prone may increase pain due to spinal hyperextension. Exercise. Simple exercises that stretch the paraspinous muscles are advocated to help reduce the pain of paraspinous muscle spasm and blunt an acute attack of low back pain. One such exercise can be performed lying supine in bed, drawing the knees up into the chest (see Fig. 147-3). However, randomized trials show inconsistent results with respect to pain and disability compared to usual care, which often includes some degree of stretching exercise. There are no clear differences among exercise regimens. Medications. NSAIDs (e.g., naproxen 500 mg BID) provide a mild to moderate reduction in acute pain and are preferred over other analgesics. In previous guidelines, acetaminophen was recommended for acute low back pain, but more recent data from well-designed studies failed to confirm significant benefit. In randomized, placebo-controlled trials, neither oxycodone/acetaminophen nor cyclobenzaprine provided any additional benefit at 1 week over a short course of NSAID therapy in patients presenting to the ER with uncomplicated low back pain. FIGURE 147-3 Initial exercise to relieve paraspinous muscle spasm. A: The patient should lie on the back and pull the knees slowly toward the chest, and hold the position for 5 minutes. B: When in severe pain, a patient may find holding the position easier lying on the side. There are limited data on use of opioids for acute nonspecific back pain, but that available suggests best use is limited to the first night or two if symptoms are incapacitating and severe enough to prevent sleep. An intermediate-strength opioid (e.g., oxycodone), often in conjunction with acetaminophen, usually suffices. Because of concern for opioid abuse, any opioid use should be restricted to only a few nights of therapy and avoided for longer-term management and in those with a history of any type of substance abuse disorder. Muscle relaxants (e.g., cyclobenzaprine [Flexeril]), which are chemically similar to the tricyclic antidepressants) are widely prescribed (13% of all acute back pain patients get a prescription). Controlled trials find modest short-term pain relief but little benefit when added to NSAID therapy. Meta-analysis suggests that cyclobenzaprine can be of help to patients in the very acute phase of illness, probably as a consequence of the drug's sedating effects. Thus, if prescribed, it should be only for a few days and best used at nighttime to avoid daytime drowsiness. Systemic glucocorticosteroids (e.g., prednisone 20 mg/d) are sometimes given with intent to reduce acute inflammation. Randomized placebo-controlled trials show little difference compared to placebo. Similarly limited results have been seen with a single intramuscular steroid injection. https://ovidsp.dc1.ovid.com/ovid-new-a/ovidweb.cgi 7/18 11/23/23, 11:09 PM Ovid: Primary Care Medicine: Office Evaluation and Management of the Adult Patient Psychotropic drugs (benzodiazepines and antidepressants) are sometimes given, but evidence of efficacy is limited and insufficient to draw any conclusions about their contribution to care. Activity Prescription and Initial Exercises Bed rest was formerly a mainstay of treatment, but, as noted, randomized trials have demonstrated that recovery is more rapid in patients who continue their ordinary activities within the limits permitted by pain. Even for patients with continuing pain and evidence of disk protrusion or extrusion, there is little evidence to support prolonged bed rest. Deconditioning with bed rest can contribute to physical and psychological morbidity. To avoid prolonged inactivity and the deconditioning that accompanies it, patients with disk protrusion or extrusion should be encouraged to begin a reasonable activity program during the first week, consisting of 20-minute walks three times a day, interspersed with several hours of bed rest. A flexion exercise can be performed (see Fig. 147-4). After the spine has healed sufficiently to allow sitting without pain, the patient can P.1241 ease into a program of endurance exercises that may help to prevent future back problems (see Prevention of Relapse), but such strengthening exercises are of no benefit during the acute phase of illness. FIGURE 147-4 In-bed flexion exercise of the lumbar spine. A: With head supported with pillow, the patient flexes the hips to 90 degrees with knees slightly flexed. The patient attempts to kick the feet over the head, raising the buttocks approximately 6 inches off resting surface. B: The patient returns feet to starting position. C: Movement is repeated for a total of five “kickups.” D: The patient lowers the legs, soles first, with knees flexed, to surface to rest. Avoid lowering the legs without bending the knees to avoid painful hyperextension strain on the spine. A reasonable program of back care should be discussed after the recovery from acute symptoms allows gradual mobilization and resumption of normal activities. The patient must understand that pain is a normal protective response to injury or inflammation. Discomfort should be used as a guideline to determine the pace at which to increase activity. However, minor discomfort, stiffness, soreness, or mild aching should not interfere with progressive mobilization. If symptoms recur or marked pain develops in relation to a specific activity or level of activity, the patient should temporarily limit activity for several days. Twisting, bending, and lifting should be avoided. If the patient undertakes a new or higher level of activity and pain increases within 24 hours, the activity should be halved each day until a tolerable level is reached and then gradually increased. The patient should be encouraged to progress as rapidly as symptoms permit. Physical Therapy Randomized, controlled trials find formal physical therapy marginally better than no treatment (e.g., an educational booklet); the cost is greater, but so is patient satisfaction. Early implementation of physical therapy results in a statistically significant improvement in disability, but the improvement is modest and does not rise to the level of clinically meaningfulness. As such, in most instances it can be held in reserve for persons who do not achieve resolution of acute symptoms, although some may benefit from the early counseling and teaching of back hygiene and basic exercises, which encourage self-care measures. Compared to spinal manipulation, functional outcomes and costs are similar. Additional Evidence-Based Nonpharmacologic Measures The costs and adverse effects of pharmacologic therapies have contributed to the popularity and appeal of nonpharmacologic measures. Popular alternative treatments sought by patients whose symptoms persist beyond a few days include chiropractic manipulation, therapeutic massage, acupuncture, and yoga. Their popularity has led to interest in formal study of their efficacy. Complicating interpretation of many early trials purporting to show efficacy was the finding that outcomes were strongly influenced by patient expectation and belief in the modality under study. As a result, more carefully conducted randomized trials using sham procedures have followed. Nonetheless, data from well-designed studies remain limited and, for some modalities, nonexistent. Most of these measures are self-prescribed and make for added expense, but could be cost saving if they reduce the need for expensive medication and days lost from work. Acupuncture. In studies comparing acupuncture with a sham procedure, there is a small, short-lived decrease in pain when used for acute back pain. When combined with NSAID therapy, there is a slight improvement in clinical course. Spinal Manipulation. Although very popular among patients, chiropractic spinal manipulation turns out to be only modestly better and short-lived in terms of functional benefit (no difference in pain) than sham therapy in randomized trials for acute nonspecific low back pain. There is no difference in pain and functional outcomes when compared to other effective conventional therapies; however, patient satisfaction is high and similar to that for physical therapy. Contraindications include presence of disk herniation, possibility of tumor, infection, compression fracture, pregnancy, previous back surgery, and neurologic deficits. Costs are high for the treatment, and no reduction in total costs has been identified. The use of a prediction rule (pain <16 days, no pain distal to the knees, one or more hypomobile lumbar segments, preserved hip internal range of motion, reduced functional capacity) has proved to be helpful in identifying persons likely to respond. Therapeutic Massage. Therapeutic massage has proved superior to control measures for acute nonspecific back pain as well as chronic back pain (see later discussion), providing both short- and long-term benefit. Benefits are observed in both pain and P.1242 functional capacity. Overall safety appears to be good, but short-term discomfort during or after a treatment is experienced by up to 15% of patients. Total costs are reduced by nearly half of patients in comparison to acupuncture and by 20% in comparison to self-care. Extrapolating from study findings to clinical practice is made somewhat difficult by the lack of standardized procedures for massage; most massage therapists perform Swedish relaxation massage. Yoga. Interest in yoga as a treatment for acute nonspecific back pain stems from its providing a combination of exercise and mental focus or meditation, well-recognized approaches to treatment of chronic pain. While there is evidence of efficacy from randomized trials in persons with chronic back pain (see later discussion), data are scarce with regards to use https://ovidsp.dc1.ovid.com/ovid-new-a/ovidweb.cgi 8/18 11/23/23, 11:09 PM Ovid: Primary Care Medicine: Office Evaluation and Management of the Adult Patient for acute nonspecific back pain. Low-Level Laser. Use of low-level laser was found in controlled study to add to pain relief and function when combined with NSAID compared to NSAID plus sham laser. Nonpharmacologic Measures without Efficacy or Devoid of Evidence A number of treatment modalities used for chronic back pain have been found to be either devoid of benefit for acute nonspecific back pain or without supporting evidence. These include spinal traction, lumbar support, topical cold, transcutaneous nerve stimulation, tai chi, Pilates, ultrasound, and taping. Disk Herniation and Discogenic Pain Overview of Approach The initial treatment for disk herniation is similar to that for acute nonspecific low back pain. Like nonspecific low back pain, pain from disk herniation tends to regress over time. Conservative therapy usually suffices, and most patients report significant improvement by 6 weeks. In those unable to tolerate symptoms, interventional measures are sometimes resorted to; however, controlled studies find little difference in pain or functional status at 1 year. Development of neurologic deficits bears watching since progression of functional loss requires consideration of interventional therapy. Only about 10% need consideration of surgery at week 6. Spinal manipulation should be avoided due to the risk of aggravating disc herniation and causing additional neurologic impairment. Checking and Monitoring for Neurologic Impairment Before proceeding with any treatment, it is important to carefully check at the outset for new or worsening neurologic deficits and continuously monitor for them, especially for symptoms and signs of cauda equina syndrome (e.g., saddle anesthesia, severe bilateral pain, numbness, weakness, bladder and bowel dysfunction), which is a neurosurgical emergency necessitating urgent MRI spinal imaging and prompt neurosurgical consultation. Initial Therapy The same basic measures used for acute nonspecific back pain (i.e., proper positioning in bed, NSAIDs, back hygiene, gentle exercise, and maintenance of activity) also serve as the foundation for initial management of pain due to disk herniation. Patients may find additional relief lying on the floor supine with their lower legs and feet resting on a cushioned chair seat (see Fig. 147-5). In some instances, adding a short course of an opioid analgesic (e.g., oxycodone for the first few days) is needed to achieve adequate pain control; a similarly short course of cyclobenzaprine or a benzodiazepine can supplement symptomatic relief and facilitate the patient's getting a night's sleep. FIGURE 147-5 Comfortable position for relief of sciatica pain. Complementary measures such as yoga, massage, and acupuncture have a less established role in the acute and subacute management of patients whose pain is related to disk herniation; spinal manipulation is of concern due to risk of exacerbating disk herniation and neurologic injury. Consequently, for persons with persistent, disabling symptoms related to disk herniation, interventional measures (epidural injection and disk surgery) deserve consideration. Interventional Procedures—Epidural Steroid Injection For patients with persistent, incapacitating radicular pain due to disk herniation who cannot hold out for spontaneous improvement, epidural glucocorticoid injection (e.g., with methylprednisolone) is a reasonable consideration for temporary relief. Under fluoroscopic guidance, a needle is inserted and advanced into the epidural space allowing injection of anesthetic and glucocorticosteroids. The use of topical anesthetic (e.g., lidocaine) helps to determine proper needle placement—immediate pain relief indicates proper positioning, but a worsening of radicular pain during the procedure is a sign of needle misplacement. The purported mechanism of pain relief involves countering inflammation associated with nerve injury, but some studies find sustained relief with anesthetic injection alone. The hypothesized inflammatory pathophysiology for sciatica and the potentially adverse effects of corticosteroids has stimulated study of other anti-inflammatory agents, particularly those that inhibit cytokines. In a randomized trial comparing epidural injection of the anti-tumor necrosis factor agent etanercept with that of glucocorticosteroid found steroid injection to be the more effective, although the difference did not achieve statistical significance. Methodology of epidural injection involves two injections typically given, spaced 3 to 4 weeks apart, with a third