CHAPTER 284 Treatment of Disk Disease of the Lumbar Spine
History
The recognition of spinal disorders has a history almost as long as written language, with early Egyptian, Greek, Roman, and Arabic texts making reference to treatment of spinal disorders as early as 1550 BCE. Hippocrates (460 BCE-377 BCE), Celsus (25 BCE-50 BCE), and Galen (131 BCE-199 BCE) developed similar methods of treating spinal fractures that included traction and immobilization.1 These methods continued to be used and taught by Chinese and Arabic practitioners and are used even today in a modified manner when treating spinal fractures nonoperatively.
Hippocrates considered the possibility of surgical treatment of paralyzed individuals with spinal fractures but did not attempt the intervention. Paulus of Aegina proposed operative repair of spine injuries in the 7th century, but spine surgery was initially undertaken in the 18th century as a means of treating tuberculous paravertebral abscesses. Progress in spine surgery was limited by high rates of postoperative infection until the ideas of Lister and Semmelweis made antisepsis standard during surgery.2
Sciatica, which describes pain originating in the back and radiating into the buttocks and legs, was recognized as being the result of an insult to the sciatic nerve by Cotugno in 1764. Definitive association with the intervertebral disk was established by the breakthrough work of Mixter and Barr in 1934. They published a small study describing symptoms that they postulated were caused by degenerative changes in the intervertebral disk that might be relieved by surgical intervention.3
Anatomy
The recurrent sinuvertebral nerve innervates the disk space area, specifically the PLL and posterior annulus. The lateral and anterior regions of the annulus are supplied by autonomic nerves. Immunohistochemical studies have demonstrated that the outer regions of the annulus are innervated but the inner regions of the annulus and the nucleus are not.4 Degenerated lumbar disks show increased innervation and vascularity.5 The bony vertebral end plate also receives a similar distribution and density of innervation.6
Interosseous tributaries from the lumbar arteries coming directly off the aorta supply the vertebral body and serve the capillary beds of the cartilaginous vertebral end plate. The disk receives most of its nutrition by diffusion from the capillary beds of the cartilaginous end plate.7
Pathophysiology
The nucleus pulposus is composed of a proteoglycan and water gel held together by an irregular network of type II collagen and elastin fibers. Aggrecan, the primary proteoglycan of the intervertebral disk, has a high concentration of both keratin sulfate and chondroitin sulfate. Sulfation of these molecules in turn provides a negatively charged molecule with the osmotic properties necessary to draw large quantities of water into the disk.8 It is the water content of the disk that allows its shock-absorbing capabilities. When the disk is loaded, water is extruded from the disk while the lateral forces are restrained by the collagen fibers of the annulus fibrosus. When the disk is unloaded, the osmotic gradient between the disk and plasma causes water to return to the disk, thereby preparing it to dissipate load forces again.
As mentioned previously, the disk is dependent on diffusion from the end plate capillary beds for acquiring nutrients and dissipating metabolites. Studies have shown that chronic lack of oxygen to the cells of the nucleus pulposus will cause the cells to become quiescent whereas lack of glucose can kill these cells.9 Because the disk is dependent on simple diffusion to meet its metabolic needs, it is very susceptible to metabolic or mechanical damage and has very limited ability to recover.10 Decreases in end plate permeability, diffusion, and hence metabolic transport are a normal function of aging. In contrast, end plate damage as a consequence of disk degeneration causes an increase in the permeability and diffusion of metabolites. This may be one way in which normal aging changes may be differentiated from pathologic degenerative changes.11
Disk cells are capable of growth and adaptive remodeling to cope with the stresses applied to them.12 Matrix is synthesized, broken down, and turned over by the actions of matrix metalloproteinases (MMPs). Studies using markers for MMPs have shown MMP levels to be highest during growth and to decline in adulthood. Degenerative disks also have high MMP levels, thus providing a possible therapeutic target.13 It has been postulated that keeping MMPs in check may minimize breakdown of the extracellular matrix in degenerative disks.14
Aging is associated with loss of proteoglycan content in the nucleus and hence water content, which decreases the ability of the disk to effectively and evenly transmit loads to the vertebral end plate.15 Loss of proteoglycan and water content may be regional, a finding suggesting focal damage and degeneration.16 At the same time, the fibers of the annulus fibrosus weaken and lose their ability to constrain the lateral forces imposed on the nucleus. It would seem, then, that the incidence of lumbar disk herniation would increase with age. This is true to a point, with the maximum incidence of lumbar disk herniation occurring in individuals 30 to 50 years of age.17 However, the incidence of lumbar disk herniation decreases after the age of 50.
There is an explanation for this seemingly paradoxical finding. The disk gradually loses its ability to expand over time. In a young person, the disk has a tremendous ability to expand, but the strong annulus fibrosus prevents excessive lateral expansion. As the annulus loses strength and the disk is still able to expand, the possibility of herniation increases during the third to fifth decades of life. After about 50 years of age, the disk begins to significantly lose its ability to expand. As a result, the incidence of disk herniation decreases despite the continued decline in annulus strength.18
Whether disk degeneration is a process different from the normal aging process or simply the normal aging process proceeding at different rates in different individuals is a controversial issue. Adams and Roughley argue that degeneration and aging are not synonymous and propose the following working definition for disk degeneration. “The process of disk degeneration is an aberrant, cell-mediated response to progressive structural failure. A degenerate disk is one with structural failure combined with accelerated or advanced signs of aging.”19 What determines whether a disk will undergo this aberrant response is a multifactorial response. Certainly, there appear to be risk factors for the development of disk degeneration and disk herniation, including driving of motor vehicles, sedentary occupations, vibration, previous full-term pregnancy, smoking, physical inactivity, increased body mass, and tall stature.20
If a degenerative disk is one suffering from structural failure, it stands to reason that mechanical loading is ultimately implicated.21 The structural disruption then initiates a cascade of biomolecular events that lead to further failure in a positive feedback loop. Degenerative disks display higher levels of MMPs, nitric oxide (NO), interleukin-6 (IL-6), and prostaglandin E2 (PGE2).22 Once again, differentiating cause and effect is difficult. Increased hydrostatic loading causes release of NO, which in turn downregulates the synthesis of proteoglycan.23 A disk with decreased proteoglycan content has decreased water content and thus decreased ability to dissipate applied forces and is more susceptible to degeneration, with further release of NO. It can be seen that this type of cascade can rapidly lead to severe pathology.
The pathophysiology of the radicular pain associated with sciatica has still not been entirely elucidated. There is, of course, an element of mechanical pressure on the nerve root, particularly in the central disk herniations responsible for cauda equina syndrome, but not all pain can be explained by mechanical pressure. It is likely that cell-mediated processes involving NO, MMPs, cytokines, and other inflammatory mediators are involved as well.24
There can be little doubt that genetic factors are also at work.25 Intervertebral disk disease shows a tremendous familial predisposition, with heritability ranging from 34% to 61%, depending on the vertebral level.26 Various alleles have been identified that may play a contributing role, including those for haplotypes of collagen,27 IL-1β,28 and aggrecan triplet-repeat polymorphisms.29 It has even been demonstrated that individuals with a certain IL-6 haplotype are far more likely to be affected with sciatica.30 Research continues in this area and will probably demonstrate links between intervertebral disk disease and many other gene polymorphisms.
Clinical Findings
It is important to keep in mind that disk degeneration is not synonymous with back pain or disk herniation. A study by Paajanen and associates demonstrated that 35% of a normal control group had substantial disk degeneration in at least one level as demonstrated by MRI.31 Miller and coworkers found a 90% incidence of disk degeneration after 50 years of age in a series of 600 autopsy specimens obtained from 273 cadavers ranging in age from infancy to 96 years.32 However, when low back pain is present in individuals with changes seen on MRI, as many as 80% of patients are able to accurately localize their pain to the appropriate level when asked to define a horizontal line across their region of greatest pain.33
Symptoms
In a patient with a herniated disk, the chief complaint is commonly leg or back pain. This pain may be associated with a recent traumatic event, but just as often the patient cannot pinpoint exactly when the pain began. After a time, the pain may begin to radiate into the hip, buttocks, or legs and may include paresthesias or weakness. The pain may be worsened by sitting, standing, pushing, pulling, bending, or twisting.33
Posterolateral disk herniation is common, perhaps because of thinning of the PLL at the periphery, and it usually affects the nerve root exiting under the pedicle of the lower vertebral body. For example, an L4-5 disk herniation usually causes signs associated with insult to the L5 nerve root. The dermatome for an L4 radiculopathy extends down the anterior aspect of the thigh and shin and across the medial part of the ankle. In contrast, radiculopathy associated with L5 tends to radiate from the posterior portion of the hip to the posterior portion of the thigh and leg, with numbness affecting the great toe and dorsal aspect of the foot. An S1 radiculopathy affects the posterior portion of the thigh and calf, with numbness of the lateral or plantar aspect of the foot.34
Differential Diagnosis
The pain and weakness that develop with radiculopathy can be caused by many conditions other than the degenerative cascade, and they also warrant consideration. Such conditions include tumors of the conus or cauda equina, diabetic amyotrophy (Bruns-Garland syndrome), osteoarthritic conditions, and synovial cysts. Imaging studies may be helpful in differentiating these entities.34
Physical Examination
Determination of spinal range of motion may be difficult because of the patient’s discomfort and associated muscle splinting. A test commonly used to elicit the patient’s pain symptoms is the straight-leg raise test or test of Lesègue. When the straight leg is elevated to an angle of 30 degrees or more, the patient’s sciatica may be reproduced on the ipsilateral side. Reproduction of pain on the contralateral side is referred to as the crossed straight-leg raise test. The straight-leg raise test is highly sensitive but not particularly specific, whereas the crossed straight-leg raise test exhibits high specificity but low sensitivity in the diagnosis of disk herniation.35 Of interest, increased PGE2 may be associated with a positive straight-leg raise test.36
Imaging
The usefulness of diskography in evaluating low back pain patients is controversial,37 and extensive debate regarding the efficacy of diskography is beyond the scope of this chapter. Diskography is probably most useful as an ancillary procedure and should be used to eliminate surgical candidates rather than include additional candidates.
Treatment Options
Nonsurgical Interventions
Nonoperative treatment is aimed at returning the patient to activities of daily living in as expedient a manner as possible. In some patients, physical restrictions may be warranted initially, but most patients eventually benefit tremendously from physical therapy and controlled exercise. The use of NSAIDs, if tolerated by the patient, is an important part of nonoperative therapy. Of note, patients whose pain is not adequately controlled by NSAIDs, narcotics, or steroids typically elect to undergo surgery. Thus, pain management is one of the most important aspects of successful nonoperative treatment.38 Nonoperative therapeutic modalities used in clinical trials include analgesics, oral or epidural corticosteroids, transcutaneous electrical nerve stimulation, physical therapy, and acupuncture.20 Even though similar outcomes may be achieved in operative and nonoperative groups within 1 year, persistent pain and dysfunction after 6 months of nonoperative therapy or any worsening of pain or dysfunction may be an indication for operative intervention.
Surgical Interventions
Indications
Patients undergoing surgery for lumbar disk herniation enjoy a high success rate with few complications.39 Recent studies have shown that perhaps many of these individuals would have recovered with nonoperative treatment and therefore might have been better off not undergoing surgery and not being exposed to the risks associated with undergoing a surgical procedure. The Maine Lumbar Spine Study showed that over a 10-year period, patients in the surgical treatment group had more complete relief of sciatica symptoms and experienced greater return to function and satisfaction than those in the nonoperative group. The caveat to this finding is that the nonoperative group over the same period reported a similar rate of remission of their primary complaint and had similar disability outcomes as their operative cohort.40
The results of the Spine Patient Outcomes Research Trial (SPORT) showed equally equivocal results. There was no significant difference in the long-term outcomes of patients with lumbar disk herniation between the operative and the nonoperative groups. These data are confounded by approximately 30% of the nonoperative group ultimately being transferred to the operative group.41 In contrast, a group in the SPORT study in which spondylolisthesis and spinal stenosis were diagnosed showed a much improved return to function and decrease in pain over a 2-year period when treated surgically. In this study also, the groups were not truly randomized inasmuch as the patients were able to switch from the surgical to the nonsurgical group and vice versa as desired.42 When patients with sciatica for a period of 6 to 12 weeks were split into operative and nonoperative groups, the return to function measured at 1 year was similar in both groups. The authors found that the surgical patients had increased satisfaction with their treatment and that maintaining patient comfort in the nonoperative group was imperative to their willingness to continue with nonoperative therapy.38
This would seem to support the notion that appropriate patient selection for operative treatment is extremely important.43 Patients in whom immediate surgical treatment should be considered include those with cauda equina syndrome and patients with profound motor weakness. Immediate intervention in these patients may improve clinical outcomes.44 Patients without severe motor deficits may initially be managed conservatively.
Technique
A typical symptomatic disk herniation may be treated with a minimal unilateral approach under magnification and the patient under general or spinal anesthesia. The nerve root is decompressed and the risk for recurrent disk herniation reduced by performing annular fenestration, curettage, and removal of loose, degenerated disk material from the disk space with a rongeur. It is often not necessary to perform a subtotal diskectomy.38
As with any spinal procedure, the side and level of disk herniation should be confirmed before beginning surgery. The specific technique used for the lumbar diskectomy depends in part on the amount and location of extruded disk material and the surgeon’s preference. In all cases, the goal of surgery is to remove compression and adequately decompress any affected nerve roots while avoiding injury to any neural structure or retroperitoneal structures on the other side of the disk space. Spinal fusion procedures are used for the treatment of several different degenerative disorders, including degenerative disk disease, disk herniation, spondylolisthesis, and stenosis. Spinal fusion procedures are indicated when increased stability and restoration of normal anatomy are required. Such procedures are increasing in the United States after the approval of various fusion devices and improvements in technique and biologics have made fusion surgery successful with few side effects.45 The primary concerns with fusion procedures are the development of pseudarthrosis and adjacent segment degeneration requiring revision. The risk for these complications increases when multiple levels are treated.
Disk replacement may be considered for individuals with degenerative disk disease and herniation without radicular pain. Disk replacement preserves motion and is not associated with increased stress at adjacent vertebral segments, in contrast to vertebral fusion procedures. The best results are achieved in younger patients and when only one vertebral level is affected.46 Exact indications for disk replacement are still controversial.
Complications
One of the most common intraoperative complications is negative exploration or wrong-level spine surgery. Although a recent survey suggested that wrong-level lumbar surgery occurs at a rate of just 4.5 per 10,000 operations, this is not insignificant.47 Ammerman and colleagues identified advancing patient age (>55 years) and pathology above the L5-S1 level as risk factors for wrong-level lumbar surgery.48 Direct preoperative communication with the patient by the surgeon, marking of the intended site, and the use of intraoperative verification radiographs have been identified as steps important in the prevention of wrong-side or wrong-level operations.49 The North American Spine Society (NASS) has developed the SMaX protocol (sign, mark, and x-ray) to assist in preventing wrong-patient, wrong-level, or wrong-surgery errors. The American Academy of Orthopedic Surgeons sponsors a similar program known as SYS (sign your site).50 Prevention of these types of errors remains a top priority.
Other intraoperative complications include violation of the dura or retroperitoneal injury. Inadvertent dural tears may occur in as many as 7.6% of lumbar spinal procedures and 15.9% of revisions. Most can be managed by repair of the defect and placement of a temporary subfascial drain, although some patients will require a return to the operating room.51 Iatrogenic vascular injury, although uncommon, may be rapidly fatal if not recognized and treated immediately.52
Postoperative complications include failure of pain relief, recurrence of pain (often from recurrent disk herniation53 or epidural scar formation), and infection.54 Recurrent disk herniation is defined as herniation and pain at the same level after 6 asymptomatic months.55 Floman and coauthors reported a nearly 14% incidence of revision surgery after lumbar diskectomy,56 whereas Connolly reported an 8% revision rate.57 Many of these revisions were required after recurrent ipsilateral disk herniation. Epidural scarring is an unavoidable consequence of any procedure in the epidural space. In most patients this scarring is clinically silent, but a few experience significant pain. The pathogenesis of this pain is postulated to be tethering of a nerve root in the foramen by scar tissue.
Infection is an uncommon but serious surgical complication. Worsening back pain often accompanied by paravertebral muscle spasm may be an indication of infection. Both the erythrocyte sedimentation rate and C-reactive protein level are elevated, with C-reactive protein being a more specific indicator of infection. Fever and leukocytosis may be absent. Treatment involves long-term antibiotic therapy and bracing, although resistant infections may require surgical débridement and instrumentation.58 Intravenous cephazolin administered prophylactically before making the skin incision has been associated with a decreased rate of postoperative infection,50 as has placement of gentamicin in the cleared disk space.59 Although there still exists some debate on the ethics and economics of prophylactic antibiotic treatment, most would agree that a single dose of prophylactic antibiotic is indicated for routine spine surgery.60
Adams MA, Freeman BJ, Morrison HP, et al. Mechanical initiation of intervertebral disc degeneration. Spine. 2000;25:1625-1636.
Adams MA, Roughley PJ. What is intervertebral disc degeneration, and what causes it? Spine. 2006;31:2151-2161.
Ammerman JM, Ammerman MD, Dambrosia J, et al. A prospective evaluation of the role for intraoperative x-ray in lumbar discectomy. Predictors of incorrect level exposure. Surg Neurol. 2006;66:470-473.
Atlas SJ, Keller RB, Wu YA, et al. Long-term outcomes of surgical and non-surgical management of sciatica secondary to lumbar disc herniation: 10 year results from the Maine Lumbar Spine Study. Spine. 2005;30:847-849.
Baldwin NG. Lumbar disc disease: the natural history. Neurosurg Focus. 2002;13(2):E2.
Biyani A, Andersson GB. Low back pain: pathophysiology and management. J Am Acad Orthop Surg. 2004;12:106-115.
Carragee EJ, Lincoln T, Parmar VS, et al. A gold standard evaluation of the “discogenic pain” diagnosis as determined by provocative discography. Spine. 2006;31:2115-2123.
Chedid KJ, Chedid MK. The “tract” of history in the treatment of lumbar degenerative disc disease. Neurosurg Focus. 2004;16(1):E1.
Davis RA. A long-term outcome analysis of 984 surgically treated herniated lumbar discs. J Neurosurg. 1994;80:415-421.
Deyo RA. Back surgery—who needs it? N Engl J Med. 2007;356:2239-2243.
Deyo RA, Gray DT, Kreuter W, et al. United States trends in lumbar fusion surgery for degenerative conditions. Spine. 2005;30:1441-1445.
Fagan A, Moore R, Vernon RB, et al. ISSLS Prize Winner: the innervations of the intervertebral disc: a quantitative analysis. Spine. 2003;28:2570-2576.
Freemont AJ, Peacock TE, Goupille P, et al. Nerve ingrowth into diseased intervertebral disc in chronic back pain. Lancet. 1997;350:178-181.
Horner HA, Urban HP. 2001 Volvo Award Winner in Basic Science Studies: effect of nutrient supply on the viability of cells from the nucleus pulposus of the intervertebral disc. Spine. 2001;26:2543-2549.
Jhawar BS, Demytra M, Duggal N. Wrong-side and wrong-level neurosurgery: a national survey. J Neurosurg Spine. 2007;7:467-472.
Kanayama M, Hashimoto T, Shigenobu K, et al. Effective prevention of surgical site infection using a Centers for Disease Control and Prevention guideline–based antimicrobial prophylaxis in lumbar spine surgery. J Neurosurg Spine. 2007;6:327-329.
Khan MH, Rihn J, Steele G, et al. Postoperative management protocol for incidental dural tears during degenerative lumbar spine surgery: a review of 3,183 consecutive degenerative lumbar cases. Spine. 2006;31:2609-2613.
Miller JA, Schmatz C, Schultz AB. Lumbar disc degeneration: correlation with age, sex, and spine level in 600 autopsy specimens. Spine. 1988;13:173-178.
Mody MG, Nourbakhsh A, Stahl DL, et al. The prevalence of wrong level surgery among spine surgeons. Spine. 2008;33:194-198.
Peul WC, van Houwelinger HC, van der Hout WB, et al. Surgery versus prolonged conservative treatment for sciatica. N Engl J Med. 2007;356:2245-2256.
Rajasekaran S, Babu JN, Arun R, et al. ISSLS Prize Winner: a study of diffusion in human lumbar discs: a serial magnetic resonance imaging study documenting the influence of the endplate on diffusion in normal and degenerate discs. Spine. 2004;29:2654-2667.
Weinstein JN, Lurie JD, Tosteson TD, et al. Surgical versus nonsurgical treatment for lumbar degenerative spondylolisthesis. N Engl J Med. 2007;356:2257-2270.
Weinstein JN, Tosteson TD, Lurie JQ, et al. Surgical vs. nonoperative treatment for lumbar disc herniation: the Spine Patient Outcomes Research Trial (SPORT): a randomized trial. JAMA. 2006;296:2441-2450.
Wera GD, Marcus RE, Ghanayer AJ, et al. Failure within one year following subtotal lumbar discectomy. J Bone Joint Surg Am. 2008;90:10-15.
Wong DA. Spinal surgery and patient safety: a systems approach. J Am Acad Orthop Surg. 2006;14:226-232.
1 Knoeller SM, Seifried C. History of spinal surgery. Spine. 2000;25:2838-2843.
2 Chedid KJ, Chedid MK. The “tract” of history in the treatment of lumbar degenerative disc disease. Neurosurg Focus. 2004;16(1):E1.
3 Mixter WJ, Barr JS. Rupture of the intervertebral disc with involvement of the spinal canal. N Engl J Med. 1934;211:210-214.
4 Palmgren T, Gronblad M, Virri J, et al. An immunohistochemical study of nerve structures in the annulus fibrosus of human normal lumbar intervertebral discs. Spine. 2001;24:2075-2079.
5 Freemont AJ, Peacock TE, Goupille P, et al. Nerve ingrowth into diseased intervertebral disc in chronic back pain. Lancet. 1997;350:178-181.
6 Fagan A, Moore R, Vernon RB, et al. ISSLS Prize Winner: the innervations of the intervertebral disc: a quantitative analysis. Spine. 2003;28:2570-2576.
7 Humzah MD, Soames RW. Human intervertebral disc: structure and function. Anat Rec. 1988;220:337-356.
8 Melrose J, Smith JM, Appleyard RC, et al. Aggrecan, versican and type VI collagen are components of annular translamellar crossbridges in the intervertebral disc. Eur Spine J. 2008;17:314-324.
9 Horner HA, Urban HP. 2001 Volvo Award Winner in Basic Science Studies: effect of nutrient supply on the viability of cells from the nucleus pulposus of the intervertebral disc. Spine. 2001;26:2543-2549.
10 Urban JP, Smith S, Fairbank JC. Nutrition of the intervertebral disc. Spine. 2004;29:2700-2709.
11 Rajasekaran S, Babu JN, Arun R, et al. ISSLS Prize Winner: a study of diffusion in human lumbar discs: a serial magnetic resonance imaging study documenting the influence of the endplate on diffusion in normal and degenerate discs. Spine. 2004;29:2654-2667.
12 Walsh AJ, Lotz JC. Biological response of the intervertebral disc to dynamic loading. J Biomech. 2004;37:329-337.
13 Antoniou J, Steffen T, Nelson F, et al. The human lumbar intervertebral disc: evidence for changes in the biosynthesis and denaturation of the extracellular matrix with growth, maturation, ageing and degeneration. J Clin Invest. 1996;98:996-1003.
14 Roberts S, Caterson B, Menage J, et al. Matrix metalloproteinase and aggrecanase: their role in disorders of the human intervertebral disc. Spine. 2000;25:3005-3013.
15 Roughley PJ. Biology of intervertebral disc aging and degeneration: involvement of the extracellular matrix. Spine. 2004;29:2691-2699.
16 Iatridis JC, MacLean JJ, O’Brien M, et al. Measurements of proteoglycan and water content distribution in human lumbar intervertebral discs. Spine. 2007;32:1493-1497.
17 Weber H. The natural history of disc herniation and the influence of intervention. Spine. 1994;19:2234-2238.
18 Kramer J. Intervertebral Disc Diseases: Causes, Diagnosis, Treatment and Prophylaxis, 2nd ed. New York: Thieme Medical; 1990.
19 Adams MA, Roughley PJ. What is intervertebral disc degeneration, and what causes it? Spine. 2006;31:2151-2161.
20 Baldwin NG. Lumbar disc disease: the natural history. Neurosurg Focus. 2002;13(2):E2.
21 Adams MA, Freeman BJ, Morrison HP, et al. Mechanical initiation of intervertebral disc degeneration. Spine. 2000;25:1625-1636.
22 Kang JD, Stefanovic-Racic M, McIntyre LA, et al. Toward a biochemical understanding of human intervertebral disc degeneration and herniation. Contributions of nitric oxide, interleukins, prostaglandin E2 and matrix metalloproteinases. Spine. 1997;22:1065-1073.
23 Liu GZ, Ishihara H, Osada R, et al. Nitric oxide mediates the change of proteoglycan synthesis in the human lumbar intervertebral disc in response to hydrostatic pressure. Spine. 2001;26:134-141.
24 Biyani A, Andersson GB. Low back pain: pathophysiology and management. J Am Acad Orthop Surg. 2004;12:106-115.
25 Virtanen IM, Karppinen J, Taimela S, et al. Occupational and genetic risk factors associated with intervertebral disc disease. Spine. 2007;32:1129-1134.
26 Kalischman L, Hunter DJ. The genetics of intervertebral disc degeneration: familial predisposition and heritability estimation. Joint Bone Spine. 2008;75:383-387.
27 Jim JJT, Noponen-Hietala N, Cheung KMC, et al. The TRP-2 allele of COL9A2 is an age-dependent risk factor for the development and severity of intervertebral disc degeneration. Spine. 2005;30:2735-2742.
28 Solovievas S, Lohiniva J, Leino-Arjas P, et al. Intervertebral disc degeneration in relation to the COL9A3 and the IL-1ss gene polymorphisms. Eur Spine J. 2006;15:613-619.
29 Solovievas S, Noponen P, Männikkö M, et al. Association between the aggrecan gene variable number of tandem repeats polymorphism and intervertebral disc degeneration. Spine. 2007;32:1700-1705.
30 Noponen-Hietala N, Virtanen I, Karttunen R, et al. Genetic variations in IL-6 associate with intervertebral disease characterized by sciatica. Pain. 2005;114:186-194.
31 Paajanen H, Erkintalo M, Kuusela T, et al. Magnetic resonance study of disc degeneration in young low-back pain patients. Spine. 1989;14:982-985.
32 Miller JA, Schmatz C, Schultz AB. Lumbar disc degeneration: correlation with age, sex, and spine level in 600 autopsy specimens. Spine. 1988;13:173-178.
33 Rengachary SS, Balabhadra RSV. Black disc disease: a commentary. Neurosurg Focus. 2002;13(2):E14.
34 Hardy RW, Ball PA. Treatment of disc disease of the lumbar spine. In Winn HR, editor: Youmans Neurological Surgery, 5th ed, Philadelphia: WB Saunders, 2004.
35 Devillé WL, van der Wint DA, Dzaferagic A, et al. The test of Lasègue: systematic review of the accuracy in diagnosing herniated discs. Spine. 2000;25:1140-1147.
36 O’Donnell JL, O’Donnell AL. Prostaglandin E2 content in herniated lumber disc disease. Spine. 1996;21:1653-1655.
37 Carragee EJ, Lincoln T, Parmar VS, et al. A gold standard evaluation of the “discogenic pain” diagnosis as determined by provocative discography. Spine. 2006;31:2115-2123.
38 Peul WC, van Houwelinger HC, van der Hout WB, et al. Surgery versus prolonged conservative treatment for sciatica. N Engl J Med. 2007;356:2245-2256.
39 Davis RA. A long-term outcome analysis of 984 surgically treated herniated lumbar discs. J Neurosurg. 1994;80:415-421.
40 Atlas SJ, Keller RB, Wu YA, et al. Long-term outcomes of surgical and non-surgical management of sciatica secondary to lumbar disc herniation: 10 year results from the Maine Lumbar Spine Study. Spine. 2005;30:847-849.
41 Weinstein JN, Tosteson TD, Lurie JQ, et al. Surgical vs. nonoperative treatment for lumbar disc herniation: the Spine Patient Outcomes Research Trial (SPORT): a randomized trial. JAMA. 2006;296:2441-2450.
42 Weinstein JN, Lurie JD, Tosteson TD, et al. Surgical versus nonsurgical treatment for lumbar degenerative spondylolisthesis. N Engl J Med. 2007;356:2257-2270.
43 Deyo RA. Back surgery—who needs it? N Engl J Med. 2007;356:2239-2243.
44 Shapiro S. Medical realities of cauda equina syndrome secondary to lumbar disc herniation. Spine. 2000;25:348-351.
45 Deyo RA, Gray DT, Kreuter W, et al. United States trends in lumbar fusion surgery for degenerative conditions. Spine. 2005;30:1441-1445.
46 Siepe CJ, Mayer HM, Wiechert K, et al. Clinical results of total lumbar disc replacement with ProDisc II: three year results for different indications. Spine. 2006;31:1923-1932.
47 Jhawar BS, Demytra M, Duggal N. Wrong-side and wrong-level neurosurgery: a national survey. J Neurosurg Spine. 2007;7:467-472.
48 Ammerman JM, Ammerman MD, Dambrosia J, et al. A prospective evaluation of the role for intraoperative x-ray in lumbar discectomy. Predictors of incorrect level exposure. Surg Neurol. 2006;66:470-473.
49 Mody MG, Nourbakhsh A, Stahl DL, et al. The prevalence of wrong level surgery among spine surgeons. Spine. 2008;33:194-198.
50 Wong DA. Spinal surgery and patient safety: a systems approach. J Am Acad Orthop Surg. 2006;14:226-232.
51 Khan MH, Rihn J, Steele G, et al. Postoperative management protocol for incidental dural tears during degenerative lumbar spine surgery: a review of 3,183 consecutive degenerative lumbar cases. Spine. 2006;31:2609-2613.
52 Bingol H, Cingoz F, Yilmaz AT, et al. Vascular complications related to lumbar disc surgery. J Neurosurg. 2004;100(3 suppl Spine):249-253.
53 Wera GD, Marcus RE, Ghanayer AJ, et al. Failure within one year following subtotal lumbar discectomy. J Bone Joint Surg Am. 2008;90:10-15.
54 Kanayama M, Hashimoto T, Shigenobu K, et al. Effective prevention of surgical site infection using a Centers for Disease Control and Prevention guideline–based antimicrobial prophylaxis in lumbar spine surgery. J Neurosurg Spine. 2007;6:327-329.
55 Suk KS, Lee HM, Moon SH, et al. Recurrent lumbar disc herniation: results of operative management. Spine. 2001;26:672-676.
56 Floman Y, Millgram MA, Smorgick Y, et al. Failure of the Wallis interspinous implant to lower the incidence of recurrent lumbar disc herniations in patients undergoing primary disc excision. J Spinal Disord Tech. 2007;20:337-341.
57 Connolly ES. Surgery for recurrent disc herniation. Clin Neurosurg. 1992;39:211-216.
58 Masuda T, Miyamoto K, Hosoe H, et al. Surgical treatment with spinal instrumentation for pyogenic spondylodiscitis due to methicillin-resistant Staphylococcus aureus (MRSA): a report of five cases. Arch Orthop Trauma Surg. 2006;126:339-345.
59 Rohde V, Meyer B, Schaller C, et al. Spondylodiscitis after lumbar discectomy. Incidence and a proposal for prophylaxis. Spine. 1998;23:615-620.
60 Mastronardi L, Tatta C. Intraoperative antibiotic prophylaxis in clean spinal surgery: a retrospective analysis in a consecutive series of 973 cases. Surg Neurol. 2004;61:129-135.
