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Percutaneous intradiskal therapies are currently used in the treatment of two distinct medical problems: chronic low back pain and the herniated nucleus pulposus–related radicular syndrome (sciatica). Both conditions lead to substantial medical and economic losses, with low back pain being the major cause of disability in the United States for patients less than 45 years of age.
The prevalence of low back pain in the general population is 60% to 80%. Low back pain is the second most common reason for work absence.
In sciatica, the complaints are the result of a protrusion of nucleus pulposus through the annulus fibrosus, causing direct compression of the exiting nerve root and subsequent radicular complaints. Although the clinical picture of sciatica differs from that of low back pain, the socioeconomic impact of both entities is of equal magnitude. The annual incidence of sciatica is 5 per 1000, making it a common problem.
The cause of both clinical entities is ascribed to disease of the intervertebral disk. This disk is a unique part of the musculoskeletal system capable of resisting axial load and rotational forces between two neighboring vertebral bodies. The disk is the largest avascular structure in the human body and consists of a cartilaginous outer margin, the annulus fibrosus, and a central gel-like structure, the nucleus pulposus. The annulus fibrosus is made up of fibrocartilaginous lamellae consisting of a.o. proteoglycans (20%) and collagen (60%, mainly type I). The outer layers of these concentric lamellae are incorporated in the posterior longitudinal ligament, resulting in a stable fixation of the disk. The junction of the disk with the vertebral bodies (synchondrosis) is made up of hyaline cartilage. The nucleus pulposus primarily consists of water (90%) and the remainder of proteoglycans (65%) and collagen (20%, mainly type II). The amount of collagen is lowest in the lumbar part of the spine. The amount of water in the nucleus pulposus varies according to a diurnal pattern and is also dependent on the mechanical forces exerted on the disk. Under normal circumstances, the disk can vary 1.2 mm in height. In degenerated disks, this might increase to 2.1 mm.
A reduction of intradiskal pressure can lead to shrinkage of the annulus fibrosus, which might result in tearing. The most important causes are a decrease in the intradiskal water content and also a decrease in the amount of proteoglycans. The proteoglycan level can decrease because of aging but is also influenced by a low intradiskal pH (in smoking) and the use of nonsteroidal anti-inflammatory drugs. Annular tears caused by aging are typically concentric in orientation as opposed to the radial tears caused by mechanical strain. Damage to the intervertebral disks can also be the result of degeneration of the vertebral bodies. Subcortical calcifications and ingrowth of bone marrow with enzyme-mediated lysis of the disk have been described as causative factors of disk damage. The innervation of the annulus fibrosus, which might be a key factor in the etiology of low back pain, was studied by Coppes and colleagues, who showed myelinated bundles of nerve fibers in the outer annulus. There are indications that in degenerative disk disease, centripetal growth of the fibers in the disk occurs, making them more vulnerable to mechanical and chemical stimulation. The chemical stimulation is attributed to cytokines (interleukin-1, -2, -8, -12, -15; interferon-α, tumor necrosis factor-α, transforming growth factor-β 1 ) and synthesis of prostaglandins released in degenerative disk disease. Weinstein and colleagues reported that the presence of neuropeptides, substance P, and vasoactive intestinal peptides influenced pain at discography.
Degeneration of the annulus fibrosus might result in a full-thickness tear, in which case the nucleus pulposus might herniate through the defect. A herniation of the nucleus pulposus might lead to compression of the exiting nerve root and hence a radicular syndrome. Risk factors for intervertebral disk herniations are familial deposition, atherosclerosis of the abdominal aorta, smoking, and repeated/prolonged vibration. The radicular complaints can be intermittent and are accredited to the changes in intradiskal pressure. The intervertebral disk can be considered as a hydraulic system in which a volume increase of merely 1.0 mL will lead to an increase of intradiskal pressure of 2340 mm Hg (312 kPa). Model calculations show pressures up to 400 mm Hg on the nerve root. This can lead to changes in blood flow and edema and subsequent changes in nerve root signal conduction. Ingrowth of blood vessels into the annulus fibrosus is observed in cases of sciatica. This is visible in 12.5% of cases with complaints of 1 month's duration and 87% with complaints lasting longer than 6 months. The clinical importance of this phenomenon is unclear. The herniated nucleus pulposus–related radicular syndrome is often accompanied by low back pain. One of the possible causes is referred pain from the recurrent sinuvertebral nerve of Luschka, which traverses one or more disk levels.
In most cases of low back pain, the pain resolves within 4 to 6 weeks with conservative first-line management, consisting of patient education, nonsteroidal anti-inflammatory drugs, and exercise regimens. However, if the pain persists despite these measures, additional medical treatment with invasive spinal procedures or intradiskal treatment is considered appropriate. This is the case in one third of patients with discogram-positive low back pain. Surgical alternatives are laminectomy, microdiskectomy, caging, or spinal fusion, of which the last is by far the primary treatment modality in the majority of patients. Risks involved with these open procedures are related to general anesthesia, nerve root damage, postoperative scar tissue formation, spinal instability, and chronic pain syndrome. In recent decades, several intradiskal therapies have been developed to provide patients with less invasive alternatives.
In 60% to 80% of patients experiencing their first episode of radicular pain, the symptoms recede to a nondisabling level within a period of 6 weeks. The remaining 20% to 40% of patients qualify for surgical intervention or less invasive intradiskal treatment modalities.
The most important treatment for sciatica is conventional diskectomy/diskotomy. This can be performed by means of a laminectomy, microdiskectomy, or even microendoscopic diskectomy. Although these open procedures are becoming less invasive over the years, minimally invasive alternatives are developed. Most of these are directed at the volume reduction of nucleus pulposus by removing intradiskal water or changing the structure of the proteins. Because the nucleus pulposus can be considered to be a hydraulic system, a small reduction of volume will result in a disproportionate pressure reduction. Hence, the herniated fragment will withdraw and the nerve root will be relieved. The change in protein structure is achieved either by applying heat or by injecting enzymes or medication and will result in a decreased capability for water resorption of the nucleus pulposus as well as a volume reduction.
The search for minimally invasive intradiskal therapies has led to a number of procedures, which are discussed here ( eTable 124-1 ).
Therapy | Technique |
---|---|
Chemonucleolysis | Chymopapain injection |
Automated percutaneous lumbar diskectomy (APLD) | |
Laser | Percutaneous laser disk decompression (PLDD), percutaneous electrothermal lumbar decompression (PELD), laser diskectomy |
Coblation | |
Intradiskal electrothermal (IDET) annuloplasty | |
Miscellaneous | Injection of alcohol, steroids, ozone/oxygen, collagenase, bupivacaine |
Chemonucleolysis is the oldest percutaneous intervention for radicular syndrome. In chemonucleolysis, a proteolytic enzyme called chymopapain is injected into the center of the intervertebral disk under fluoroscopic guidance to induce hydrolysis of the proteoglycan molecules that form the nucleus pulposus. The fact that the resulting proteoglycan fragments have limited water-binding abilities leaves intradiskal water molecules free to diffuse into the surrounding tissues. The resulting loss of water causes a decrease of intradiskal pressure. The chymopapain molecules remain attached to the proteoglycan fragments, permanently limiting the ability of the nucleus pulposus to attract water. In addition to its proteolytic effects on nucleus pulposus tissue, chymopapain is also postulated to have anti-inflammatory properties, directly inhibiting the proinflammatory enzyme phospholipase A 2 .
Lumbar radicular syndrome with evidence on discography of contained lumbar disk herniation
Insufficient reaction to at least 6 weeks of adequate conservative management
Sequestration
Severe neurologic symptoms that require acute surgical intervention (cauda equina syndrome, severe paresis)
Severe disk space narrowing (50%)
Obstructive vertebral abnormalities (e.g., spondylosis, facet hypertrophy)
Previous disk surgery at the same level
Active infection (e.g., systemic infection, infection of the intervertebral disk space or puncture site)
Pregnancy
Coagulopathy
Spinal tumor
Fracture
Allergic sensitivity to papain or papaya
Previous injection of chymopapain
18-gauge needle
Lidocaine, 0.5%
Deionized, water-soluble contrast medium
C-arm fluoroscope
Chymopapain (currently out of production)
Chemonucleolysis requires posterolateral access to the nucleus pulposus of the affected disk, under biplanar fluoroscopic guidance. The patient is placed in a lateral decubitus position with a pillow placed in the flank to correct unwanted spine curvatures. The puncture site is identified by marking a point 8 to 10 cm from the spinous process at the level of the diseased disk. After preparation of the patient under sterile conditions, including local anesthesia of skin and underlying muscles, an 18-gauge needle is introduced under fluoroscopic guidance. The correct position of the needle tip inside the nucleus pulposus is verified in both transverse and sagittal planes. Lumbar discography is performed to ascertain the integrity of the disk. Subsequently, 1 to 2 mL of chymopapain solution is slowly injected into the nucleus pulposus.
Careful monitoring of patient reaction and the appropriate use of visual guidance are crucial to prevent damage to nerve roots and surrounding tissues during needle placement or subsequent treatment. As in all percutaneous procedures, there is always a risk of inoculation of microorganisms into the center of the intervertebral disk, with resulting diskitis. Taking appropriate antiseptic measures during the procedure can minimize this risk. The use of additional antibiotic prophylaxis may further reduce the risk of septic diskitis, although this is not supported by the literature. Some authors report the use of a double-needle technique, in which a (slightly curved) 22-gauge needle is introduced through an 18-gauge needle. This approach is said to facilitate needle placement in cases of obstruction by a broad transverse process at L5 and is postulated to reduce the chance of intradiskal infection, because the 22-gauge needle has not been contaminated by skin bacteria.
Chemonucleolysis may well be the most controversial minimally invasive percutaneous treatment for lumbar radicular syndrome. Publications on serious complications such as cauda equina syndrome and severe anaphylactic reactions have overshadowed its clinical benefits. Skin tests may be used to trace sensitization for chymopapain-like substances, in order to prevent anaphylactic reactions. The use of prophylactic histamine-1 and histamine-2 blockers has also been suggested to lower the risk of anaphylactic reactions, although it is not supported by literature and may cause unwanted sedative side effects.
The use of discography before chymopapain injection is essential to rule out loss of disk integrity, because extradiskal leakage of chymopapain could cause severe damage to adjacent structures. Low back spasm is a benign but painful complication of chemonucleolysis. Some authors claim reduction in back pain after lowering the amount of chymopapain that is injected into the disk, whereas others advocate the injection of bupivacaine during needle withdrawal. Administration of intravenous corticosteroids just before chymopapain injection might prevent anaphylactic reactions.
Numerous clinical trials, including several prospective randomized placebo-controlled, double-blinded trials, have been conducted to assess the efficacy of chemonucleolysis. These studies have shown beneficial effects of chemonucleolysis, with long-term success rates of up to 80% in properly selected patients.
Enzyme leakage into extradiskal tissue has been reported, with the possibility of damage to nerve roots, dural sac, or spinal cord. Severe anaphylactic reactions have been reported in 0.2% to 0.5% of patients, dropping to 0% to 0.25% if preoperative skin test screening is performed to track chymopapain sensitization. The overall mortality rate after chymopapain injection is approximately 1 in 5000 patients (0.02%). Transient low back spasms are a frequent (20% to 40%) complication of chemonucleolysis, which can be quite severe in 10% of patients. Other potential complications inherent in the nature of the procedure are nerve root damage, spondylodiskitis, hemorrhage, or allergic reactions to local anesthetics.
The risk of life-threatening complications, although significantly lower than for conventional disk surgery, has damaged the reputation of chemonucleolysis. As a result of the decreasing popularity of chemonucleolysis among centers in the United States, the manufacturer of Chymodactin (a new formulation of chymopapain) ceased production in October 1999, ending its worldwide clinical use.
Chemonucleolysis, being a minimally invasive spinal intervention, is performed on an outpatient basis. Postoperatively, patients are permitted walking, sitting, and standing activities, in concordance with normal daily activities. No specific follow-up care is necessary after chemonucleolysis. There is no indication for physical therapy.
Automated percutaneous lumbar diskectomy (APLD) is a minimally invasive intervention in which nucleus pulposus material is mechanically removed using an automated nucleotome, designed by Onik and associates in 1985. The initial results of the first series of patients were presented in 1987. The automated nucleotome is a 2-mm blunt-tipped device equipped with a reciprocating suction cutter. The nucleotome is introduced through a 2.5-mm diameter cannula into the center of the nucleus pulposus, where nucleus pulposus material is cut and aspirated at a rate of 180 times per minute. The resulting loss of nucleus pulposus mass causes a drop in intradiskal pressure.
Lumbar radicular syndrome with MRI evidence of contained lumbar disk herniation
Insufficient reaction to at least 6 weeks of adequate conservative management
Disk extrusion or sequestration
Severe neurologic symptoms that require acute surgical intervention (e.g., cauda equina syndrome, severe paresis)
Severe disk space narrowing (50%)
Disk herniation (50% of spinal canal)
Obstructive vertebral abnormalities (e.g., spondylosis, facet hypertrophy)
Previous disk surgery at the same level
Active infection (e.g., systemic infection, infection of the intervertebral disk space or puncture site)
Pregnancy
Coagulopathy
Spinal tumor
Fracture
Automated nucleotome (probe and cutting/suction device) (Claris Lifesciences, Eatontown, N.J.)
18-gauge introduction trocar
Tissue dilator
Cutting cannula
Trephine
CT scanner (optional)
Lidocaine, 0.5%
C-arm fluoroscope
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