Lumbar Prolapse Intervertebral Disc

                   Lumbar Prolapse Intervertebral Disc

                                                 Dr. KS Dhillon

Anatomy of the Disc

The human spinal column has 23 fibrocartilage intervertebral discs. There are 6 in the cervical column, 12 in the thoracic, and 5 in the lumbar column. Each disc is a few millimeters thick and it lies between adjacent surfaces of the vertebrae. The discs make up roughly a quarter [1] to a third [2] of the height of the column.

The disc is formed of peripheral fibrous cartilage called the annulus fibrosus which surrounds a centrally located gelatinous core known as the nucleus pulposus. In adults, there is no clear boundary between the nucleus and the annulus within the disc. Superiorly and inferiorly the nucleus pulposus is coated by cartilage endplates.

The endplate is usually less than 1 mm thick. It contains horizontal collagen fibers that run parallel to the vertebral bodies and eventually become continuous with the disc.

Annulus fibrosus

The annulus fibrosus is a strong radial tire-like structure that contains fibroblast that constantly synthesizes type I and II collagen into lamellar fibers, forming concentric rings, or lamellae [2]. The lamellae are interconnected by bundles of smaller fibers which consist of fibrillin, lubricin, elastin, aggrecan, and type VI collagen [3]. 

The lamellae of the annulus are thicker anteriorly and on the lateral sides. Posteriorly the lamellae are finer and more tightly packed [4]. This probably accounts for the fact that most often the nucleus pulposus protrudes posteriorly. 

Between the lamellae are elastin fibers that bind the lamella together. Most of these elastin fibers are concentrated near the attachment of the annulus fibrosus to the vertebral endplate. The elasticity provided by this elastin becomes reduced with aging. The stress and strain placed on the annulus results in small fissures with loss of interwoven collagen fibers. This results in the tearing and extrusion of parts of the nucleus.

The annulus has two distinct layers, the inner and outer annulus fibrosus. The inner layer contains an extracellular matrix composed of type II collagen, proteoglycans, and water. The cells of the inner annulus are oval-shaped. The outer layer is rich in type I collagen and has a higher resistance to tension.

Sixty to seventy of the annulus is water. The water content gradually decreases with age. 

Nucleus pulposus

The typical nucleus pulposus consists of a semi-fluid mass of mucoprotein ground substance and it occupies about 40% of the disc’s cross-sectional area. It contains a few chondrocyte-like cells, collagen fibers, elastin fibers, and aggrecan-containing gel [4]. The chondrocyte-like cells produce type II collagen and proteoglycans.

The nucleus is usually situated between the middle and posterior thirds of the disc. The nucleus pulposus has 70-90% water content which decreases with age. The proteoglycans interact with water and resist compression. The aggrecan is primarily responsible for maintaining the water content of the disc.

Vertebral Endplate

The vertebral endplates are situated at the cranial and caudal ends of the intervertebral disc. The endplates are usually less than 1 mm in thickness. The endplates are made up of both hyaline cartilage and fibrocartilage. The endplates prevent the nucleus pulposus from herniating into the adjacent vertebrae.

Vertebral endplates also contain high concentrations of proteoglycans, water (50-60%), and type II collagen fibers. Along the collagen fibers, there are cartilage cells.

The loss of proteoglycans with age from the endplate cartilage is associated with the loss of proteoglycans from the nucleus pulposus. The depletion of proteoglycans eventually leads to intervertebral disc degeneration.

Blood Supply

The adult nucleus pulposus and inner annulus fibrosus have no blood supply and are completely avascular. There are, however, a few blood vessels around the peripheral annulus. These peripheral annulus and endplate capillaries come from segmental arteries, which are branches of the aorta. These capillaries provide nutrients to the region of the outer annulus fibrosus. This blood then drains into the subchondral venous plexus and into the veins of the marrow of the adjacent vertebral body [3].

Nutrition to the nucleus pulposus reaches through diffusion through pores in the vertebral endplates.

Innervation

Only the outer annulus fibrosus is innervated by sensory and sympathetic perivascular nerve fibers, from the grey rami communicantes, branches from the sinuvertebral nerve, or from the ventral rami of spinal nerves. Beyond the superficial fibers, there is no innervation. Neuropeptides thought to participate in the sensory transmission include substance P, calcitonin, vasoactive intestinal polypeptide, neuropeptide Y, C-flanking peptide, and synaptophysin [3].

Lumbar Intervertebral Discs

There are five intervertebral discs in the lumbar region the lowest of which sits atop the sacrum. The lumbar discs are taller and wider than the cervical and thoracic disc. The lumbar disc measures about 7–10 mm in thickness and 4 cm in diameter (AP plane) [2]. The discs are cylindrical in shape. The anterior height of the lumbar discs is greater than the posterior height and this is especially noticeable in the fifth lumbar disc. This shape of the disc is responsible for the lordosis especially In the upper segment of the lumbar spine. In the lower lumbar regions, the shape of the vertebral body is a contributing factor [1].

Lumbar radiculopathy can result from chemical irritation from proteoglycan released from the disc due to degeneration and fissuring of the disc. This release creates an inflammatory reaction from the exposed disc tissue leading to radiculopathy.

The spinal nerve roots leave the dural sac just above the level of each intervertebral foramen. The lumbar nerves lie sufficiently high in the foramina and they are usually unaffected by a degenerated disc at the same level unless segments of the disc migrate cranially. Hence, the fifth lumbar nerve root is more likely to be compressed by an L4-L5 disc than by a L5-S1 disc [1]. About 40% of intervertebral disc abnormalities affect the fourth and fifth lumbar nerve roots [5].

Biomechanics of the intervertebral disc

The function of the disc is to maintain flexibility and motion. The facet joints and disc are responsible for carrying the compressive loads and stresses the spine is subjected to. Some of these loads and stresses include static loads, dynamic loads, tensile stresses, shear stresses, torsional loads, and a combination of tensile, compressive, and shear stresses.

The annulus carries the tensile stresses and the nucleus carries the compressive loads. This changes when disc degeneration occurs when the hydration of the disc is less, then the tensile stresses in the collagen fibers of the annulus become compressive stresses. The stress distributions inside the degenerated disc changes as compared to healthy disc. The intradiscal pressure is position-dependent. It is lowest when lying supine, intermediate when standing and the pressure is highest when sitting and flexed forward with weights in the hands.

Pathophysiology of intervertebral disc degeneration and prolapse

There are several factors that are believed to influence the etiology of disc degeneration. These include age, genes, mechanical factors, such as compressive loading, shear stress, and vibration as well as systemic and toxic factors. 

1.Ageing

As the disc ages changes occur in the disc. There is an impaired synthesis of the matrix and the cell concentration declines especially in the annulus.

The proteoglycans synthesis rate also declines with a decline in the concentration of proteoglycans in the nucleus. There is a decline in link proteins and type IX collagen which leads to the production of proteoglycans which are smaller and less aggregated. The concentration of chondroitin sulfate also falls. An increase in collagen and a change from type II to type I collagen makes the nucleus more fibrous. The nucleus and annulus merge. There is less binding of water and the nucleus becomes more solid, dry, and granular with cracks in the fibrous nucleus. The lamellae of the annulus increase in thickness and become more fibrillated. Cracks and cavities develop in the annulus. Declining nutrition, accumulation of degraded matrix products, cell senescence, and fatigue failure of the nucleus may be the cause of these changes.

Aging intervertebral discs lose their ability to proliferate. There is decreased anabolism or increased catabolism in the senescent cells. An increased degree of senescence leads to disc herniation [6].

2.Genetic factors

A genetic predisposition to disc degeneration has been shown by studies in twins.

A study by Videman et al [7] showed that specific vitamin D receptor alleles were associated with intervertebral disc degeneration. They showed for the first time the existence of genetic susceptibility to progressive, age-related degenerative disease of the spine.

Several studies have implicated, the Taq I and Fok I of the vitamin D receptor gene, in disc degeneration [7,8,9]. The prevalence of the t-allele of Taq I differs among races, and hence the risk for disc degeneration also differs. It is present in about 8% Asians, 31% of Africans, and 43% of Caucasians [10]. 

In the elderly but not in the young, the 5A allele is a probable risk factor for accelerated degenerative changes of lumbar discs [11]. Trp2 and Trp3 alleles can cause substitution of the amino acids in type IX collagen by tryptophan. Patients with such types of collagen are at a higher risk for lumbar disc degeneration and sciatica [12,13]. The tryptophan-containing type IX collagen gene is believed to produce an unstable triple helix which makes the disc more susceptible to mechanical stress [14]. Trp3 is present in 24% of Finnish patients with disc degeneration but is absent in southern Chinese. Trp2 occurs in 20% of southern Chinese patients with disc degeneration but in only 4% of Finnish patients who have sciatica [13]. 

3.Nutrition

The intervertebral disc is to a large extent avascular. It is the largest avascular tissue in the body. The adult nucleus pulposus and inner annulus fibrosus have no blood supply and are completely avascular. There are a few blood vessels around the peripheral annulus. The blood vessels come from segmental arteries, which are branches of the aorta.

The outer annulus obtains nutrition directly from the blood vessel and the inner annulus and nucleus pulposus obtain nutrition through diffusion from the blood vessels. Reduction in the diffusion of nutrients can lead to disc degeneration.

Atheromatous lesions in the abdominal aorta, as well as congenital hypoplasia of the lumbar arteries, can cause disc degeneration [15,16,17]. The capillary network at the periphery of the disc diminishes after the first 10 years of life and that's when the first signs of disc degeneration become obvious [18,19].

With age, calcification of the endplate occurs which occludes the vascular opening within it, thereby blocking the transport of nutrients to the disc. Smoking causes vasoconstriction which leads to anoxia of the cells in the disc and therefore smoking is associated with an increased incidence of disc herniation and disc degeneration [20,21].

4.Metabolic disorders

Metabolic disorders can cause disc degeneration. In patients with alkaptonuria, there is intradiscal deposition of black pigment which can induce disc degeneration.

In diabetic patients, there is an increase in hydroxyproline and inactivity of enzymes involved in the metabolism of carbohydrates with a decrease in hexosamine content [22]. There are deficiencies in the incorporation of 35S-sulphate during proteoglycan synthesis in the disc. This disturbs the normal biochemistry of matrix synthesis and that can lead to disc degeneration. 

5.Toxic factors

Animal studies show that nicotine directly inhibits the proliferation of disc cells as well as the synthesis of the extracellular matrix [23]. Passive smoking leads to the downregulation of collagen genes which leads to degenerative histologic changes in the disc [24].

6.Autoimmune theory

Antigenic components of the nucleus pulposus can enter the circulation if there is damage to the endplate after a spinal compression injury. This antigenic material can trigger an immune response that produces a chronic inflammatory reaction leading to disc resorption at the affected level or may sometimes involve discs at different vertebral levels, leading to multilevel degeneration [25].

Experiments in animals show that a break in the physiological barrier of the disc by injury can alter the role of  Fas ligand in the disc leading to apoptosis of the disc cells [26]. 

7.Low-grade infection

Stirling et al [27] developed a new serological test which they used to diagnose deep-seated infections that were caused by low virulent gram-positive microorganisms. Forty-three of their 140 patients (31%) with sciatica, tested positive. Intervertebral disc material from 36 patients with severe sciatica who had microdiscectomy was cultured. Fifty-three percent of these patients had positive cultures after long-term incubation. Propionibacterium acnes was grown from 16 of the 19 (84%) positive cultures. They believed that low virulent microorganisms, in particular P acnes, might be causing a low-grade infection in the intervertebral discs of patients with severe sciatica. They were of the opinion that the microorganisms could have gained access to the disc from previous trauma.

8.Mechanical factors

Aihara et al [28] carried out a study to determine the influence of the lumbosacral transitional vertebra on disc degeneration. By using MRI they found that the lumbar discs which were immediately above the transitional vertebra had significantly more degeneration as compared to those between the transitional vertebrae and the sacrum, which had far less degeneration.

They also performed an anatomical study in 70 cadavers and they found that the iliolumbar ligament at the level immediately proximal to the transitional vertebra was thinner and weaker than it was in cadavers without a lumbosacral transitional vertebra. They concluded that the morphology of the iliolumbar ligament was involved in degeneration associated with a lumbosacral transitional vertebra [28]. This evidence shows that mechanical factors are involved in the aetiology of disc degeneration. 

Animal [29] and human [30] studies show that mechanical factors do produce disc degeneration adjacent to a lumbar fusion.

9.Compression

Although the lumbar discs are designed to sustain compression loads which are beneficial to the disc, excessive loading can be harmful to the disc. Loading provides a stimulus for matrix turnover [31]. Excessive loading reduces gene expression of anabolic proteins which has significant effects on aggrecan formation [32].

Compression forces lead to endplate damage which leads to depressurization of the nucleus and it increases stress in the posterior annulus [33]. The inner lamellae of the annulus begin to buckle inward and the outer lamellae buckle outwards because the depressurized nucleus is no longer able to brace the annulus. The interlaminar shear stresses are highest in the posterolateral annulus. These stresses lead to concentric tears in the annulus fibrosus [34].

Compression and endplate injuries can lead to biochemical changes in the matrix of the disc. The biosynthetic activity of cells in the disc is affected and there is an inflammatory response leading to degradation of the disc. 

10.Torsion

Torsional movements of the spine can damage the collagen fibers in the annulus. When the spine is flexed the facet joints permit rotation which allows stretching of the fibers leading to annular tears [35]. 

11.Vibration

Vibrations that match the resonant frequency of the lumbar spine (4 Hz to 6 Hz) can affect the nutrition [36] and metabolism [37] of the disc leading to disc degeneration.

Drivers of tractors, buses, trucks [38,39,40,41], and helicopter pilots [42] are exposed to whole-body vibrations. These people have been found to have a high incidence of back pain. 

There is some evidence to show that there is a high incidence of disc herniation in occupational drivers [43,44,45].

Disc degeneration is not a clinical diagnosis. It is an expression of the condition of the disc. Degeneration of the disc is caused by several factors acting collectively or individually. 

Most people believe that disc degeneration is the result of age-related changes. This belief is based on circumstantial evidence only. 

There is increasing evidence that disc degeneration is caused by mechanical factors. Injury to the vertebral endplate is central to the degenerative process. Compressive loading or torsion can cause fractures of the endplate and tears of the annulus. 

Endplate fractures and disc degeneration do not occur due to a single traumatic event. Repeated subliminal insults to the disc cause these endplate fractures and disc degeneration.

The disc degeneration eventually leads to a decrease in height of the disc with collapse of intervertebral space and the formation of osteophytes.

Clinical Presentation

Symptoms 

Pain is usually the chief complaint in patients with prolapsed disc. The pain is radicular but may be axial. It is more typically, radicular. It is useful to obtain information regarding the character of the pain, whether it is sharp, burning, or prickling in nature because such pain is usually due to nerve root irritation. It is important to know about the onset of pain, is it acute, subacute, or chronic.

Besides the pain, it is pertinent to know whether there are symptoms of motor weakness, sensory disturbances, and bladder or bowel dysfunction.   A progressive neurologic deficit is seen in patients with cauda equina syndrome which is a surgical emergency. 

The pain, sensory disturbances, and weakness are in the distribution of one or more lumbosacral nerve roots. The leg pain increases with straining, coughing, and sneezing. The pain increases when sitting because when we are sitting the disc pressure increases by nearly 40% [46].

Signs

When doing physical examination, the first indication that a patient may have a lumbar disk prolapse comes from the patient's gait. Patients with a prolapsed disc have a sciatic list. A sciatic list is an attempt to relieve the neuromeningeal tension on the nerve root by drawing the nerve root away from the prolapsed disc. When the herniation is lateral to the nerve root  (called a shoulder disc) the patient leans away from the side of the herniation. When the herniation is medial to the nerve root (called an axillary disk) the patient leans towards the side of the herniation. The examination may also show paraspinal muscle spasm with obliteration of the central furrow.

Lasegue sign or Straight Leg Raising Test (SLRT) is a neurodynamic examination which is commonly used to assess nerve root irritation in the lumbosacral area. The test is performed with the patient supine and the lower limb is slowly raised by holding the ankle with the knee fully extended. Once the pain is elicited further leg elevation is stopped. The criteria for a true positive SLRT [47,48] is that the pain should radiate below the knee and that the pain occurs between 30 and 60 or 70 degrees from the horizontal.

The accuracy of SLRT can be better if it is interpreted with other nerve root tests. These include:

• Cross SLRT[49]: This test is also known as a well-leg raising test or Fajersztajn sign. This test is performed by raising the contralateral lower limb and the pain is felt on the affected side. This test is much more specific than ipsilateral SLRT. It is usually positive in patients with severe compression from a centrally located disc prolapse.  
• Reverse SLRT[50]: Also known as femoral stretch or Ely test. It is performed with the patient in a prone position and the lower limb is lifted off the table with both the hip and knee joints extended. When the test is positive it produces pain in the distribution of the femoral nerve. It is positive in patients with upper lumbar radiculopathy, far lateral lumbar disc prolapse, or femoral neuropathy. 
• Braggard test [51]: It is also known as sciatic stretch test or flip test. This test is performed by dorsiflexion of the ankle while the SLRT is performed and is positive when the pain in the leg increases on doing the test. 
• Reverse flip test: While doing the SLRT, plantarflexion of the ankle, will lessen the pain. If, on the other hand, the patient complains of more pain, it is likely that the patient is malingering.
• Bowstring sign[52]: This test is also known as the popliteal compression test or posterior tibial nerve stretch sign. In performing this test the examiner flexes the knee and applies pressure on the posterior tibial nerve in the popliteal fossa, evoking sciatica. 

Following inspection, palpation, and examination maneuvers a meticulous neurologic examination is carried out which will confirm the nerve root that is involved. In paracentral disc herniations, the traversing nerve root is affected while in far lateral disc herniations, the exiting nerve root is affected. A paracentral herniation at L4-5 would cause L5 radiculopathy and a far lateral herniation at the same level would cause L4 radiculopathy.

Manual muscle testing, sensory testing, and supine SLR test with its crossed leg variant are the gold standard for clinical diagnosis of LDH according to the North American Spine Society’s (NASS) Evidence-Based Guideline Development Committee. Tests such as the cough impulse test, femoral nerve stress test, hyperextension test, range of lumbar motion, and absence of reflexes are not clinically helpful. 

A meta-analysis by Petersen et al [53] concluded that screening by SLR test with three of the following four symptoms in a nerve root distribution was sufficient for clinical diagnosis of lumbar disc herniation with radiculopathy: dermatomal pain, reflex deficit, sensory deficits, and/or motor weakness.

Imaging

1.Radiographs

The first line imaging modality used for patients with low back pain is plain radiographs.  In the absence of a neurological deficit, there is no need for radiographs in the first 6 to 12 weeks. When radiographs are taken, besides the AP and lateral views flexion and extension views should also be taken to assess spinal instability. Features suggestive of a herniated disc include compensatory scoliosis, narrowed disc space, and the presence of osteophytes [54].

2.Magnetic Resonance Imaging

Magnetic resonance imaging (MRI) is the gold standard for imaging to confirm the presence of a herniated disc. It has a diagnostic accuracy of 97% and high inter-observer reliability [55]. The presence of an increased T2-weighted signal in the posterior 10% of the disc diameter is highly suggestive of disc herniation [56]. MRI is not indicated for all patients with disc herniation. Indications for an MRI in the early period of disc herniation (< 6 weeks) include the presence of neurologic deficits and cauda equina syndrome.

3.Computed Tomography

Computed tomography (CT) was in the past clinically inferior to MRI in the detection of a herniated disc. This, however, has now changed with the introduction of the multidetector CT (MDCT) [57,58]. Now the diagnostic accuracy of CT is nearly equal to that of MRI [57,58]. The use of CT myelography is recommended when MRI is unavailable or cannot be used because of pacemakers or cochlear implants, and in patients who are excessively uncomfortable due to claustrophobia or intractable pain.

Treatment

Disc prolapse is common and it can be seen in up to a quarter of MRI scans. Disc prolapse can also be seen in asymptomatic individuals [59]. 

When confronted with a symptomatic patient with a prolapsed disc the question that comes to the mind is, what is the best treatment for lumbar disc herniation?

Non-operative treatment

Symptomatic patients with disc herniation can be treated conservatively without surgery. Conservative non-operative treatment is the treatment of choice for the majority of the patients.

A multimodal approach consisting of anti-inflammatory medications, education, and physical therapy forms the basis of non-operative management [60]. The radicular pain due to lumbar disc herniation (LDH) should improve within six to eight weeks with conservative management [61].

Nonsteroidal anti-inflammatory drugs such as ibuprofen are commonly used to treat patients with disc prolapse. Tramadol can be added if there is insufficient pain relief. Patients with more substantial pain can be treated with mild narcotic pain medication, such as hydrocodone-acetaminophen. Physiotherapy can be started which would include exercises, core strengthening, and joint mobility. Pain relief modalities, such as ultrasound, ice and heat pack therapy, whirlpool, electrical stimulation, and massage can be added 

Epidural steroid spinal injections are widely used to treat back pain and radiculitis. According to Dr. Deyo, despite the increase in the use of steroid spinal injections for back pain more patients are reporting functional and work limitations, rather than less patients [62]. He also cited a University of Washington study which showed that seven clinical trials found injections to be useful, another seven trials found that injections were no better or even worse than a placebo, and in three trials the outcome was unclear [63]. 

Epidural/transforaminal injections are associated with a wide variety of complications which include: Infection (discitis, osteomyelitis, epidural abscess, meningitis), intravascular injections (7.9-11.6%), epidural hematoma (0-1.9%), nerve and neurological injury leading to paralysis/quadriplegia, adhesive arachnoiditis, blindness, intravascular injections (7.9-11.6%), air embolism, urinary retention, CSF fistulas (up to 6%), persistent headaches (28%), allergic reactions, seizures and even death [62].

In 2014 FDA warned that injections of corticosteroids into the epidural space of the spine can result in rare but serious adverse effects, including stroke, loss of vision, paralysis, and death [64].

Saal and Saal [65] in a retrospective study reported that 90% of their 64 patients had a good or excellent outcome with conservative treatment at an average follow-up of 31.1 months. 

Spontaneous regression of symptomatic lumbar disc herniation (SLDH) is known to occur. Wang et al [66] carried out a systematic review and meta-analysis to study the incidence of regression after the non-surgical treatment of symptomatic lumbar disc herniation. They found that the overall incidence of regression was 63% in non-surgically treated SLDH patients. Based on their review, they suggested a follow-up timeline with time points 4 months and 10.5 months after the onset of symptoms when deciding whether to perform surgery for SLDH. They concluded that surgery can be performed in patients with severe symptoms who do not experience regression after 4 months of onset. They strongly recommended surgery for patients who do not experience regression after 10.5 months of onset.

Gugliotta et al [67] carried out a study to compare the effectiveness of surgical and conservative treatment in patients with symptomatic lumbar disc herniation. They found that the medium and long-term ( at 12 weeks to 52 weeks) outcomes for conservative and surgical treatment of (LDH) were similar.

Operative treatment

Operative treatment is essential in patients with progressive neurologic deficits, saddle anesthesia, and in those with bowel or bladder involvement. Patients with paresthesias or motor weakness with radicular pain may be candidates for surgery if conservative treatment fails. Patients with symptoms present for greater than six months may be candidates for surgical treatment [68].

Surgical treatment of herniated disc, in several studies, have shown

improved short-term benefits. In the medium to long-term, the value of surgery is not so clear with conflicting reports in the literature [69,70,71]. 

Osterman et al [72] carried out a randomized study comparing non-operative treatment with microdiscectomy for LHD. They found no clinically significant differences between the groups as far as leg or back pain intensity, subjective disability, or health-related quality of life was concerned at a 2-year follow-up. There was a more rapid initial recovery with discectomy. 

The outcome after discectomy is good in patients with higher severity of leg pain, severe preoperative low back pain, good mental health status, younger age, shorter symptom duration, and increased preoperative physical activity [73,74,75].

Postoperative outcomes are not affected by the presence of motor deficit, gender of the patient, vertebral level, or side of herniation, and the presence of type I Modic changes [54].

There are several approaches used for the surgical treatment of LDH. These include:

Minimally Invasive Surgery.

Minimally invasive surgery of the spine was introduced to reduce soft tissue and bony trauma and decrease hospital stay. Minimally invasive surgery is performed by using percutaneous endoscopic approaches to LDH which include transforaminal, posterolateral, interlaminar, and transiliac approaches [76,77]. 

A systematic review and meta-analysis comparing minimally invasive surgery with open discectomy by Phan et al [78] showed that

endoscopic discectomy is associated with decreased operative time as well as less blood loss when compared to open discectomy. The complication rates, reoperation rates, or wound infection rates were similar in the two groups. The postoperative leg pain scores and the postoperative Oswestry disability index scores were the same in the two groups.

A double-blind randomized control trial by Overdevest et al [79] failed 

to detect a difference between minimal invasive discectomy with tubular retractors and open microdiscectomy when long-term patient-centered outcomes were measured.

Choi et al [80] carried out a retrospective review of 149 patients who underwent percutaneous endoscopic lumbar discectomy (PELD) for a migrated herniated disc. They found that the outcome was favorable in 90.6% of the cases. In patients with high-grade disc herniations with upward migration of the disc, they found a 13% rate of remnant disc fragment and a 3% rate of revision surgery.

Bai et a [81] carried out a study to compare the outcome of L5-S1 discectomy by a transiliac approach and conventional transforaminal approach. They found no significant differences in outcome between the two groups. 

Although the interlaminar approach has the advantage that endoscopic guidance can be directly inserted, the approach, however, has the disadvantage that the nerve root and thecal sac has to be retracted which can be a challenge in patients with a large disc herniation [77]. 

The available data, of long term outcome after minimally invasive surgery, is conflicting in nature and is limited. 

Li et al [82] showed a 93% 5-year patient satisfaction rate in 134 patients who underwent combined percutaneous endoscopic lumbar discectomy (PELD) and percutaneous lumbar foraminoplasty (PLF). Tu et al [83] showed a 90% 5 years satisfaction rate in patients who underwent full-endoscopic interlaminar discectomy (FEID) and in patients who underwent microendoscopic discectomy (MED). 

There were dural tears in 5.9% of the patients, 1.3% had reoperation for hematoma and infection, 8.55% had recurrence out of which 1.9% require spinal fusion.

Eun et al [84] reported a 9.6% revision rate at the same level in 62 patients who underwent percutaneous endoscopic lumbar discectomy (PELD). This study had 11 years of follow up.

The risk factors for failure after PELD include central disc herniation, obesity, age > 50 and surgeon inexperience [54].

Open Discectomy

There are large studies such as the SPORT [85] and Maine trials [86] that have demonstrated the efficacy of open discectomy in LDH. 

The paracentral disc herniation is usually approached via the paracentral approach and the far lateral herniations are approached via Wiltse’s approach between the multifidus and longissimus muscles.

The main concern with open discectomy have been the risk of infection affecting the clinical outcome. Prolonged duration (more than 68 mins) of operation and absence of prophylactic antibiotics are known risk factors for infection [87].

There have been suggestions in recent literature that the risk of postoperative infection is higher in patients who receive lumbar epidural injections. A study by Seavey et al [88] showed that there is no significant difference in infection rate in patients who had an epidural infection and those who did not have an epidural injection before the disc surgery.  

Kotil et al [89] carried out a study to evaluate the use of close suction drains in patients undergoing single-level lumbar discectomy. With MRI done postoperatively on days 1, 180, and 365, they found that there were significantly higher rates of epidural hematoma and epidural fibrosis in patients where no drains were used.

A study by Murphy et al [90] showed that the use of a microscope during open discectomy was associated with an increase in operating time. 

Complications of discectomy

There are several complications which are associated with lumbar discectomy including dural tears, nerve root injury, new or worsening neurological deficit, wound complications (infection, dehiscence, or seroma), hematoma, worsening of functional status, and recurrent disc herniation. 

The incidence of dural tears following LDH surgery ranges from 1 to 17%. The incidence is higher in patients with obesity, advanced age, and in those undergoing revision procedures [91]. Dural tears are associated with higher hospitalization costs and increased incidence of wound dehiscence (2.4 times higher) [91].

The incidence of post-operative infection ranges from 1–5% and worsening of functional status can be seen in about 4% of the patients [89,90].

New or worsening neurological deficit can be seen in about 1.3% to 3.0% of the patients and direct nerve root injury in about 0.9% to 2.6% of the patients [92]. Hematomas develop in 0.5% to 1.2% of the patients [92]. The incidence of recurrent disc complications is between 3.1% to 4.4% and the incidence of reoperation is between 3.7%, to 10.2% [92].

There are several risk factors for recurrent herniation and these include, trauma, older age, pre-operative disc height index, smoking, disc protrusion, disc sequestration, workers’ compensation, longer duration of sick leave, diabetes, and greater preoperative symptom severity [75, 93,94,95,96,97,98]. 

The complication rates following discectomy are no different in patients with and without restriction of activity following the surgery [99]. Therefore there is no reason to restrict activity after surgery which should allow patients to return to work earlier.

Failed back surgery syndrome (FBSS)

Failed back surgery syndrome (FBSS) refers to the failure of back surgery to satisfactorily improve the patient’s symptoms. It is usually characterized by intractable pain and varying degrees of functional disability following lumbar spine surgery.

It is estimated that 10% to 40% of patients who undergo back surgery develop FBSS after lumbar spine surgery [100]. 

In the USA statistics suggest that there are 25,000 to 50,000 cases of failed back syndrome per year [101]. It is a major public health problem and probably the greatest single waste of health care resources in the USA [101]. In the UK there are around 2000 cases of failed back surgery syndrome each year [102]. For microdiscectomy, the failure rates are between 19% to 25% [103].

FBSS following disc surgery is known as post-discectomy-syndrome (PDS). Some of the causes of poor results after lumbar disc surgery include postoperative instability of the spine, recurrent disc herniation,    entrapment of the spinal nerve roots by scar tissue, arachnoiditis, psychological syndromes, and insurance-related issues[104]. 

Surgery for PDS is only indicated in patients with recurrent disc herniation and spinal instability. In all other situations surgery is not indicated and if surgery is carried out the patient's symptoms may worsen [104].

There are several modalities of non-surgical treatment FBSS [105]. These include:

• Nonsteroidal anti-inflammatory drugs--The first line of treatment includes the use of nonsteroidal anti-inflammatory drugs (NSAIDs). Oral NSAIDs have been shown to be effective for persistent low back pain [106]. A recent Cochrane review, however, highlighted the lack of NSAID efficacy in chronic radicular pain [107]. In recent years the use of Cox 2 inhibitors has gained ground. There are, however, no human studies that have shown the advantage of Cox 2 inhibitors over other NSAIDs [108].
• Paracetamol+tramadol---Paracetamol has been used in the treatment of spinal pain. A recent meta-analysis by Machado et al [109] has shown that paracetamol is not effective in reducing pain and disability in patients with chronic back pain. A combination of paracetamol with tramadol is considered an efficient approach to the management of patients with low back pain [110]. 
• Muscle relaxants ---Thiocolchicoside a semi-synthetic derivative of colchicines has an affinity for the inhibitory glycine and gamma-aminobutyric acid (GABA)-A receptors and have glycomimetic and Gaba mimetic activity which produces muscle relaxant action. Muscle relaxation reduces back pain caused by excessive muscle spasm. The clinical efficacy of thiocolchicoside has been demonstrated in many clinical trials [111].  Thiocolchicoside produces muscle relaxation without any objective or subjective sedative side-effects.[112]. There are, however, no randomized trials to show the efficacy of muscle relaxants in the treatment of chronic low back pain [105].
• Opioids and their derivatives ---Opioids and their derivatives are frequently used in the management of FBSS. Tramadol and codeine which are weak opioid agonists do help improve pain and disability, particularly in the elderly patients. They are not associated with gastrointestinal side effects of NSAIDs and renal toxicity [113]. Major oral opiates such as morphine, oxycodone, and methadone can be used in patients with refractory pain. A combination of oxycodone and naloxone has better analgesic efficacy than oxycodone alone or morphine. The risk of constipation is lower with oxycodone and naloxone combination [114]. The risk of dependence can be reduced with careful prescriptions. 
• Antidepressants and antiepileptics---Many patients with FBSS have some element of depression and hence antidepressants such as duloxetine, amitriptyline, and venlafaxine are often used. These drugs also have analgesic effects [115]. Antiepileptics drugs such as pregabalin and gabapentin are often used to treat the neuropathic component of pain [116]. These drugs must be gradually introduced to prevent somnolence and dizziness. There was a recent randomized controlled trial that showed the ineffectiveness of gabapentin for analgesia in chronic low back pain and radicular pain [118]. 
• Spinal infiltration---Epidural steroids have been in the past used to treat FBSS. Epidural steroids provide short-term pain relief and improvement in activity levels. There is always a risk of infection with epidural infection in fragile patients using corticosteroids. In several patients, serious neurological complications, including paraplegia has been reported following lumbar epidural injections. Rare but serious risks of neurological complications such as loss of vision, stroke, paralysis, and sometimes death have been reported following epidural injection and the USA FDA has declared an alert and label change for injectable long term corticosteroids [119].
• Spinal cord stimulation---Spinal cord stimulation (SCS) was initially used for the treatment of neuropathic and radicular pain in patients who had failed to improve with other therapies. Now it is increasingly being used to treat FBSS.  There is now strong evidence for the efficacy of SCS in properly selected patients with FBSS [120]. For spinal cord stimulation electrodes are implanted in the epidural space and electrical current is produced by a pulse generator placed under the skin [120]. The analgesia produced by SCS is believed to occur via a gate-control mechanism and modulation of excitatory and inhibitory neurotransmitter release which occurs in the dorsal horn [120].
• Exercise Therapy/Physiotherapy---Patients with FBSS have weakness of the abdominal and paraspinal muscles which stabilizes the spine. Hence exercises to strengthen these muscles are useful in the treatment of FBSS. These exercises help to reduce pain, improve posture and fitness, stabilize the hypermobile segments of the spine, and reduce mechanical stress on the spine [121]. Patients are also taught active coping mechanisms for the pain [120]. Literature review shows that there are several exercise programs described but unfortunately there is no evidence to show the superiority of one program over another in terms of outcome [122]. A systematic by Hayden et al [123] identified the important components of an exercise program. They found that an individualized exercise program composed of supervision, strengthening, and stretching was associated with superior outcomes. Core muscle strengthening exercises of the trunk muscles have been shown to improve spinal stability and reduce pain [124]. A Cochrane review by Hayden et al [125] showed that in adults with chronic low back pain, exercise therapy appears to be slightly effective in decreasing pain and improving function.  This finding has been supported by 2 other systematic reviews [126,127]. 
• Psychological Therapy----Psychological factors are involved in the pathogenesis of FBSS. Therefore psychological therapy constitutes one arm of treatment of FBSS. Broadly, psychological therapy consists of behavioral (BT) and cognitive-behavioral treatment (CBT). In BT-CBT psychological principles are applied to change the thoughts, overt behavior and feelings of patients with chronic pain. This helps them experience less distress and make their lives more satisfying and productive [128]. BT-CBT also reduces the patients' pain and improves their daily functioning. In CBT patients are taught relaxation skills; goal setting and pacing strategies; perception changing strategies such as visual imagery, desensitization, hypnosis and promotion of self-management perspective. Recent reviews support the effectiveness of CBT in patients with chronic pain [129-133].

Conclusion

Low back pain is very common and the most common source of this pain is intervertebral degeneration leading to degenerative disc disease and lumbar disc herniation (LDH). Over the years substantial advancements have been made in understanding the cause of LDH as well as in the diagnosis, imaging, and treatment options available for patients with lumbar disc herniation (LDH).

The treatment of choice in the majority of patients with symptomatic LDH is non-operative management. In the event of failure of conservative treatment, surgery is usually recommended. There are several studies that have shown improved short-term benefits of surgical treatment but in the medium, to long term, the value of surgery is not so clear.

The complications after surgery can be as high as 17% and between 10% to 40% of the patients can develop failed back syndrome which can be very difficult to treat.

   

 

References

1. DePalma AF, Rothman RH. The Intervertebral Disc. Philadelphia, PA: W.B. Saunders Company; 1970.
2. Urban JP, Roberts S. Degeneration of the intervertebral disc. Arthritis Res Ther. 2003;5(3):120-130.
3. Tomaszewski KA, Saganiak K, Gładysz T, Walocha JA. The biology behind the human intervertebral disc and its endplates. Folia Morphol (Warsz). 2015;74(2):157-168.
4. Bogduk N. Clinical Anatomy of the Lumbar Spine and Sacrum. 3rd ed. New York, NY: Churchill Livingstone; 1997.
5. Dutton M. Orthopaedic Examination Evaluation and Intervention. 2nd ed. New York, NY: McGraw-Hill Global Education Holdings; 2008.
6. Hadjipavlou AG, Tzermiadianos MN, Bogduk N, Zindrick MR. The pathophysiology of disc degeneration. A critical review. The Journal of Bone and Joint Surgery. British volume. Vol. 90-B, No. 10.
7. Videman T, Leppävuori J, Kaprio J, et al. Intragenic polymorphisms of the vitamin D receptor gene associated with intervertebral disc degeneration. Spine 1998;23:2477–85.
8. Kawaguchi Y, Kanamori M, Ishihara H, et al. The association of lumbar disc disease with vitamin-D receptor gene polymorphism. J Bone Joint Surg [Am] 2002;84-A:2022–8.
9. Cheung KMC, Chan D, Karppinen J, et al. Association of the Taq I allele in vitamin D receptor with degenerative disc disease and disc bulge in Chinese. Spine 2006;31:1143–8.
10. Uitterlinden AG, Fang Y, Van Meurs JB, Pols HA, Van Leeuwen JP. Genetics and biology of vitamin D receptor polymorphisms. Gene 2004;338:143–56.
11. Takahashi M, Haro H, Wakabayashi Y, et al. The association of degeneration of the intervertebral disc with 5a/6a polymorphism in the promoter of the human matrix metalloproteinase-3 gene. J Bone Joint Surg [Br] 2001;83-B:491–5.
12. Paassilta P, Lohiniva J, Goring HH, et al. Identification of a novel common genetic risk factor for lumbar disk disease. JAMA 2001;285:1843–9. 
13. Annunen S, Paassilta P, Lohiniva J, et al. An allele of COL9A2 associated with intervertebral disc disease. Science 1999;285:409–12. 
14. Persikov AV, Ramshaw JA, Brodsky B. Collagen model peptides: sequence dependence of triple-helix stability. Biopolymers 2000;55:436–50.
15. Kauppila LI. Can low-back pain be due to lumbar-artery disease? Lancet 1995;346:888–9. 
16. Kauppila LI, Tallroth K. Postmortem angiographic findings for arteries supplying the lumbar spine: their relationship to low-back symptoms. J Spinal Disord 1993;6:124–9. 
17. Kauppila LI, McAlindon T, Evans S, et al. Disc degeneration/back pain and calcification of the abdominal aorta: a 25-year follow-up study in Framingham. Spine 1997;22:1642–9. 
18. Boos N, Weissbach S, Rohrbach H, et al. Classification of age-related changes in lumbar intervertebral discs. Spine 2002;27:2631–44.
19. Chandraraj S, Briggs CA, Opeskin K. Disc herniations in the young and end-plate vascularity. Clin Anat 1998;11:171–6.
20. Kelsey JL, Githens PB, O’Connor T, et al. Acute prolapsed lumbar intervertebral disc: an epidemiological study with special reference to driving automobiles and cigarette smoking. Spine 1984;9:608–13. 
21. Battie MC, Videman T, Gill K, et al. Smoking and lumbar intervertebral disc degeneration: an MRI study of identical twins. Spine 1991;16:1015–21.
22. Aufdermaur M, Fehr K, Lesker P, Silberberg R. Quantitative histochemical changes in intervertebral discs in diabetes. Exp Cell Biol 1980;48:89–94.
23. Akmal M, Kesani A, Anand B, et al. Effect of nicotine on spinal disc cells: a cellular mechanism for disc degeneration. Spine 2004; 29:568–75.
24. Uei H, Matsuzaki H, Oda H, et al. Gene expression changes in an early stage of intervertebral disc degeneration induced by passive cigarette smoking. Spine 2006;31:510–14.
25. Gertzbein SD, Tile M, Gross A, Falk R. Autoimmunity in degenerative disc disease of the lumbar spine. Orthop Clin North Am 1975;6:67–73.
26. Wang J, Tang T, Yang H, et al. The expression of Fas ligand on normal and stabbed-disc cells in a rabbit model of intervertebral disc degeneration: a possible pathogenesis. J Neurosurg Spine 2007;6:425–30.
27. Stirling A, Worthington T, Rafiq M, Lambert PA, Elliott TS. Association between sciatica and Propionibacterium acnes. The Lancet 2001;357:2024–5.
28. Aihara T, Takahashi K, Ogasawara A, et al. Intervertebral disc degeneration associated with lumbosacral transitional vertebrae: a clinical and anatomical study. J Bone Joint Surg [Br] 2005;87-B:687–91.
29. Phillips FM, Reuben J, Wetzel FT. Intervertebral disc degeneration adjacent to a lumbar fusion. An experimental rabbit model. J Bone Joint Surg Br. 2002 Mar;84(2):289-94.
30. Lee CK. Accelerated degeneration of the segment adjacent to a lumbar fusion. Spine (Phila Pa 1976). 1988 Mar;13(3):375-7. 
31. Handa T, Ishihara H, Ohshima H, et al. Effects of hydrostatic pressure on matrix synthesis and matrix metalloproteinase production in the human lumbar intervertebral disc. Spine 1997;22:1085–91.
32. Neidlinger-Wilke C, Würtz K, Urban JP, et al. Regulation of gene expression in intervertebral disc cells by low and high hydrostatic pressure. Eur Spine J 2006;15(Suppl 3):372–8.
33. Adams MA, McNally DS, Wagstaff J, Goodship AE. Abnormal stress concentrations in lumbar intervertebral discs following damage to the vertebral bodies: a cause of disc failure? Eur Spine 1993; 1:214–21.
34. Vernon-Roberts B, Fazzalari NL, Manthey BA. Pathogenesis of tears of the annulus investigated by multiple-level transaxial analysis of the T12-L1 disc. Spine 1997;22:2641–6.
35. Adams MA, Hutton WC. The mechanical function of the lumbar apophyseal joints. Spine 1983;8:327–30.
36. Holm S, Nachemson A. Nutrition of the intervertebral disc: effects induced by vibration. Orthop Trans 1985;9:525. 
37. Kelsey JL, Githens PB, O’Connor T, et al. Acute prolapsed lumbar intervertebral disc: an epidemiological study with special reference to driving automobiles and cigarette smoking. Spine 1984;9:608–13.
38. Frymoyer JW, Pope MH, Costanza MC, et al. Epidemiologic studies of low-back pain. Spine 1980;5:419–23. 
39. Kelsey JL. An epidemiological study of acute herniated lumbar intervertebral discs. Rheumatol Rehabil 1975;14:144–59. 
40. Kelsey JL. An epidemiological study of the relationship between occupations and acute herniated lumbar intervertebral discs. Int J Epidemiol 1975;4:197–205. Crossref,
41. Bovenzi M, Zadini A. Self-reported low back symptoms in urban bus drivers exposed to whole-body vibration. Spine 1992;17:1048–59.
42. Bongers PM, Hulshof CT, Dijkstra L, et al. Back pain and exposure to whole body vibration in helicopter pilots. Ergonomics 1990;33:1007–26.
43. Kelsey JL, Hardy RJ. Driving of motor vehicles as a risk factor for acute herniated lumbar intervertebral disc. Am J Epidemiol 1975;102:63–73. 
44. Heliövaara M. Occupation and risk of herniated lumbar intervertebral disk and sciatica leading to hospitalization. J Chron Dis 1987;40:259–64. 
45. Jensen MV, Tüchsen F, Ørhedem E. Prolapsed cervical intervertebral disc in male professional drivers in Denmark, 1981 – 90: a longitudinal study of hospitalizations. Spine 1996;21:2352–55.
46. Nachemson A. Disc pressure measurements. Spine (Phila Pa 1976). 1981;6(1).
47. Dyck P. Lumbar nerve root: the enigmatic eponyms. Spine. 1984 Jan-Feb;9(1):3-6.
48. Supik LF, Broom MJ. Sciatic tension signs and lumbar disc herniation. Spine. 1994 May 01;19(9):1066-9.
49. Hudgins WR. The crossed straight leg raising test: a diagnostic sign of herniated disc. J Occup Med. 1979 Jun;21(6):407-8.
50. Estridge MN, Rouhe SA, Johnson NG. The femoral stretching test. A valuable sign in diagnosing upper lumbar disc herniations. J. Neurosurg. 1982 Dec;57(6):813-7.
51. Vroomen PC, de Krom MC, Knottnerus JA. Consistency of history taking and physical examination in patients with suspected lumbar nerve root involvement. Spine (Phila Pa 1976). 2000 Jan;25(1):91-6; discussion 97. 
52. Supik LF, Broom MJ. Sciatic tension signs and lumbar disc herniation. Spine. 1994 May 01;19(9):1066-9.
53. Petersen T, Laslett M, Juhl C. Clinical classification in low back pain: best-evidence diagnostic rules based on systematic reviews. BMC Musculoskelet Disord. 2017;18(1):188. 
54. Amin RM, Andrade NS, Neuman BJ. Lumbar Disc Herniation. Curr Rev Musculoskelet Med. 2017;10(4):507-516. 
55. Kim KY, Kim YT, Lee CS, Kang JS, Kim YJ. Magnetic resonance imaging in the evaluation of the lumbar herniated intervertebral disc. Int Orthop. 1993;17(4):241-4. 
56. Messner A, Stelzeneder D, Trattnig S, et al. Does T2 mapping of the posterior annulus fibrosus indicate the presence of lumbar intervertebral disc herniation? A 3. 0 Tesla magnetic resonance study. Eur Spine J. 2017;26:877–883.
57. Janssen ME, Bertrand SL, Joe C, Levine MI. Lumbar herniated disk disease: comparison of MRI, myelography, and post-myelographic CT scan with surgical findings. Orthopedics. 1994;17(2):121–127. 
58. Notohamiprodjo S, Stahl R, Braunagel M, et al. Diagnostic accuracy of contemporary multidetector computed tomography (MDCT) for the detection of lumbar disc herniation. Eur Radiol. 2017 Aug;27(8):3443-3451.
59. Boden S. The use of radiographic imaging studies in the evaluation of patients who have degenerative disorders of the lumbar spine. J Bone Joint Surg Am 1996;78:114-25.
60. Wong J, Cote P, Sutton DA, et al. Clinical practice guidelines for the noninvasive management of low back pain: a systematic review by the Ontario Protocol for Traffic Injury Management (OPTIMa) Collaboration. Eur J Pain. 2017;21:201–216.
61. Fairbank J. Prolapsed intervertebral disc [published correction appears in BMJ. 2008 Jul 2;337:a649. doi.10.1136/bmj.a649]. BMJ. 2008;336(7657):1317-1318. 
62. Epstein NE. The risks of epidural and transforaminal steroid injections in the Spine: Commentary and a comprehensive review of the literature. Surg Neurol Int. 2013;4(Suppl 2): S74-S93. 
63. American Medical Association Morning Rounds, in Affiliation with Bulleting HEALTHCARE, CDC: 25 dead in meningitis outbreak, cases reach 337 in 18 states. Monday, October 29, 2012
64. FDA. Press Release: FDA Drug Safety Communication: FDA requires label changes to warn of rare but serious neurologic problems after epidural corticosteroid injections for pain. April 23, 2014. Available at: https://www.fda.gov/Drugs/DrugSafety/ucm394280.htm.
65. Saal JA, Saal JS. Nonoperative treatment of herniated lumbar intervertebral disc with radiculopathy. An outcome study. Spine (Phila Pa 1976). 1989 Apr;14(4):431-7.
66. Wang Y, Dai G, Jiang L, Liao S. The incidence of regression after the non-surgical treatment of symptomatic lumbar disc herniation: a systematic review and meta-analysis. BMC Musculoskelet Disord. 2020 Aug 10;21(1):530. 
67. Gugliotta M, da Costa BR, Dabis E, et al. Surgical versus conservative treatment for lumbar disc herniation: a prospective cohort study. BMJ Open. 2016;6(12).
68. Schoenfeld AJ, Weiner BK. Treatment of lumbar disc herniation: Evidence-based practice. Int J Gen Med. 2010;3:209-214. 
69. Weinstein JN, Tosteson TD, Lurie JD, et al. Surgical vs nonoperative treatment for lumbar disk herniation. JAMA. 2006;296(20):2441. 
70. Atlas SJ, Deyo RA, Keller RB, Chapin AM, Patrick DL, Long JM, Singer DE. The Maine lumbar spine study part II: 1-year outcomes of surgical and non-surgical management of sciatica. Spine (Phila Pa 1976) 1996;21(15):1777–1786.
71. Atlas SJ, Keller RB, Wu YA, Deyo RA, Singer DE. Long-term outcomes of surgical and nonsurgical management of lumbar spinal stenosis: 8 to 10 year results from the Maine lumbar spine study. Spine (Phila Pa 1976). 2005 Apr 15;30(8):936-43. 
72. Osterman H, Seitsalo S, Karppinen J, Malmivaara A. Effectiveness of microdiscectomy for lumbar disc herniation. Spine (Phila Pa 1976) 2006;31(21):2409–2414.
73. Oba H, Takahashi J, Tsutsumimoto T, et al. Predictors of improvement in low back pain after lumbar decompression surgery: prospective study of 140 patients. J Orthop Sci. 2017:6–11. 
74. Tschugg A, Lener S, Hartmann S, et al. Preoperative sport improves the outcome of lumbar disc surgery: a prospective monocentric cohort study. Neurosurg Rev. 2017; 
75. Wilson CA, Roffey DM, Chow D, Alkherayf F, Wai EK. A systematic review of preoperative predictors for postoperative clinical outcomes following lumbar discectomy. Spine J. 2016; 16(11): 1413–1422.
76. Bai J, Zhang W, Wang Y, et al. Application of transiliac approach to intervertebral endoscopic discectomy in L5/S1 intervertebral disc herniation. Eur J Med Res. 2017;22(14):4–13. 
77. Tonosu J, Oshima Y, Shiboi R, Hayashi A, Takano Y, Koga H. Consideration of proper operative route for interlaminar approach for percutaneous endoscopic lumbar discectomy. J Spine Surg. 2016;2(4):281–288.
78. Phan K, Xu J, Schultz K, Alvi MA, Lu VM, Kerezoudis P, Maloney PR, Murphy ME, Mobbs RJ, Bydon M. Full-endoscopic versus micro-endoscopic and open discectomy: A systematic review and meta-analysis of outcomes and complications. Clin Neurol Neurosurg. 2017 Mar;154:1-12.
79. Overdevest GM, Peul WC, Brand R, Koes BW, Bartels RH, Tan WF, Arts MP; Leiden-The Hague Spine Intervention Prognostic Study Group. Tubular discectomy versus conventional microdiscectomy for the treatment of lumbar disc herniation: long-term results of a randomised controlled trial. J Neurol Neurosurg Psychiatry. 2017 Dec;88(12):1008-1016. 
80. Choi KC, Lee DC, Shim HK, Shin SH, Park CK. A Strategy of Percutaneous Endoscopic Lumbar Discectomy for Migrated Disc Herniation. World Neurosurg. 2017 Mar;99:259-266. 
81. Bai J, Zhang W, Wang Y, An J, Zhang J, Sun Y, Ding W, Shen Y. Application of transiliac approach to intervertebral endoscopic discectomy in L5/S1 intervertebral disc herniation. Eur J Med Res. 2017 Apr 4;22(1):14. doi: 10.1186/s40001-017-0254-0. Erratum in: Eur J Med Res. 2017 Jul 5;22(1):22. PMID: 28376859; PMCID: PMC5379676.
82. Li ZZ, Hou SX, Shang WL, Song KR, Zhao HL. Modified Percutaneous Lumbar Foraminoplasty and Percutaneous Endoscopic Lumbar Discectomy: Instrument Design, Technique Notes, and 5 Years Follow-up. Pain Physician. 2017 Jan-Feb;20(1): E85-E98. PMID: 28072800.
83. Tu Z, Li YW, Wang B, Lu G, Li L, Kuang L, Dai Y. Clinical Outcome of Full-endoscopic Interlaminar Discectomy for Single-level Lumbar Disc Herniation: A Minimum of 5-year Follow-up. Pain Physician. 2017 Mar;20(3): E425-E430. PMID: 28339442.
84. Eun SS, Lee SH, Sabal LA. Long-term Follow-up Results of Percutaneous Endoscopic Lumbar Discectomy. Pain Physician. 2016 Nov-Dec;19(8): E1161-E1166. PMID: 27906946.
85. Lurie JD, Tosteson TD, Tosteson AN, et al. Surgical versus nonoperative treatment for lumbar disc herniation: eight-year results for the spine patient outcomes research trial (SPORT) [published correction appears in Spine (Phila Pa 1976). 2015 Jan;40(1): E59]. Spine (Phila Pa 1976). 2014;39(1):3-16. 
86. Atlas SJ, Keller RB, Wu YA, Deyo RA, Singer DE. Long-term outcomes of surgical and nonsurgical management of sciatica secondary to a lumbar disc herniation: 10 year results from the Maine lumbar spine study. Spine (Phila Pa 1976). 2005 Apr 15;30(8): 927-35. 
87. Habiba S, Nygaard ØP, Brox JI, Hellum C, Austevoll IM, Solberg TK. Risk factors for surgical site infections among 1,772 patients operated on for lumbar disc herniation: a multicentre observational registry-based study. Acta Neurochir (Wien). 2017 Jun;159(6):1113-1118.
88. Seavey JG, Balazs GC, Steelman T, Helgeson M, Gwinn DE, Wagner SC. The effect of preoperative lumbar epidural corticosteroid injection on postoperative infection rate in patients undergoing single-level lumbar decompression. Spine J. 2017 Sep;17(9):1209-1214. 
89. Kotil K. Closed Drainage versus Non-Drainage for Single-Level Lumbar Disc Surgery: Relationship between Epidural Hematoma and Fibrosis. Asian Spine J. 2016 Dec;10(6):1072-1078. 
90. Murphy ME, Hakim JS, Kerezoudis P, Alvi MA, Ubl DS, Habermann EB, Bydon M. Micro vs. macrodiscectomy: Does use of the microscope reduce complication rates? Clin Neurol Neurosurg. 2017 Jan;152:28-33. 
91. Puvanesarajah V, Hassanzadeh H. The true cost of a dural tear. Spine (Phila Pa 1976) 2017;42(10):770–776.
92. Shriver, M. F., Xie, J. J., Tye, E. Y., Rosenbaum, B. P., Kshettry, V. R., Benzel, E. C., & Mroz, T. E. (2015). Lumbar microdiscectomy complication rates: a systematic review and meta-analysis, Neurosurgical Focus FOC, 39(4), E6. Retrieved Nov 5, 2020, from https://thejns.org/focus/view/journals/neurosurg-focus/39/4/article-pE6.xml.
93. Shin B-J. Risk factors for recurrent lumbar disc herniations. Asian Spine J. 2014;8(2).
94. Huang W, Han Z, Liu J, Yu L, Yu X. Risk factors for recurrent lumbar disc herniation. Medicine (Baltimore) 2016;95(2):1–10. 
95. Cinotti G, Roysam GS, Eisenstein SM, Postacchini F. Ipsilateral recurrent lumbar disc herniation. A prospective, controlled study. J Bone Jt Surg. 1993;80-B:825–832. 
96. 98. Kim K, Park S, Kim Y. Disc height and segmental motion as risk factors for recurrent lumbar disc herniation. Spine (Phila Pa 1976) 2009;34(24):2674–2678. 
97. Belykh E, Krutko AV, Baykov ES, Giers MB, Preul MC, Byvaltsev VA. Preoperative estimation of disc herniation recurrence after microdiscectomy: predictive value of a multivariate model based on radiographic parameters. Spine J. 2017;17(3):390–400. 
98. Hegarty D, Shorten G. Multivariate prognostic modeling of persistent pain following lumbar discectomy. Pain Physician. 2012;15(5):421.
99. Carragee EJ, Han MY, Yang B, Kim DH, Kraemer H, Billys J. Activity restrictions after posterior lumbar discectomy: a prospective study of outcomes in 152 cases with no postoperative restrictions. Spine (Phila Pa 1976) 1999;24(22):2346–2351.
100. Thomson S, Jacques L. (2009). Demographic Characteristics of Patients with Severe Neuropathic Pain Secondary to Failed Back Surgery Syndrome. Pain Practice 9, 206–215.
101. Heithoff KB, Burton CV. CT evaluation of the failed back surgery syndrome. Orthop Clin North Am. 1985 Jul;16(3):417-44. PMID: 3159991.
102. Talbot L. "Failed back surgery syndrome". BMJ. 2003;327(7421):985-986. doi:10.1136/bmj.327.7421.985.
103. Chan CW, Peng P. Failed back surgery syndrome. Pain Med 2011; 12(4): 577–606.
104. Marchetti PG, Binazzi R, Vaccari V, De Zerbi M, Landi S. Failed back syndromes: opinions and personal experiences. Chir Organi Mov. 1994 Jan-Mar;79(1):127-30. English, Italian. PMID: 8076470.
105. Sebaaly A, Lahoud MJ, Rizkallah M, Kreichati G, Kharrat K. Etiology, Evaluation, and Treatment of Failed Back Surgery Syndrome. Asian Spine J. 2018;12(3):574-585. doi:10.4184/asj.2018.12.3.574.
106. Wong JJ, Cote P, Ameis A, et al. Are non-steroidal anti-inflammatory drugs effective for the management of neck pain and associated disorders, whiplash-associated disorders, or non-specific low back pain?: a systematic review of systematic reviews by the Ontario Protocol for Traffic Injury Management (OPTIMa) Collaboration. Eur Spine J. 2016;25:34–61. 
107. Roelofs PD, Deyo RA, Koes BW, Scholten RJ, van Tulder MW. Non-steroidal anti-inflammatory drugs for low back pain. Cochrane Database Syst Rev. 2008;(1):CD000396. 
108. Van Dijk B, Potier E, Licht R, Creemers L, Ito K. The effect of a cyclooxygenase 2 inhibitor on early degenerated human nucleus pulposus explants. Global Spine J. 2014;4:33–40.
109. Machado GC, Maher CG, Ferreira PH, et al. Efficacy and safety of paracetamol for spinal pain and osteoarthritis: systematic review and meta-analysis of randomised placebo controlled trials. BMJ. 2015; 350:h1225.
110. Tetsunaga T, Tetsunaga T, Tanaka M, Ozaki T. Efficacy of tramadol-acetaminophen tablets in low back pain patients with depression. J Orthop Sci. 2015;20:281–6.
111. Kumar S, Rani S, Siwach R, Verma P. To compare the efficacy and safety of fixed dose combination of thiocolchicoside and aceclofenac versus chlorzoxazone, aceclofenac and paracetamol in patients with acute lower backache associated with muscle spasm. Int J Appl Basic Med Res. 2014;4:101–5.
112. Patat A, Klein MJ, Surjus A, Renault M, Rezvani Y, Granier J. Effects of acute and repeated doses of two muscle relaxants chlormezanone and thiocolchicoside, on vigilance and psychomotor performance of healthy volunteers. Hum Psychopharmacol. 1991;6:285–92.
113. Imamura T. Significant Efficacy of Tramadol/Acetaminophen in Elderly Patients with Chronic Low Back Pain Uncontrolled by NSAIDs: An Observational Study. Open Orthop J. 2015 May 15;9:120-5. doi: 10.2174/1874325001509010120. PMID: 26157527; PMCID: PMC4484344.
114. Ueberall MA, Mueller-Schwefe GH. Safety and efficacy of oxycodone/naloxone vs. oxycodone vs. morphine for the treatment of chronic low back pain: results of a 12 week prospective, randomized, open-label blinded endpoint streamlined study with prolonged-release preparations. Curr Med Res Opin. 2015;31(7):1413-29. doi: 10.1185/03007995.2015.1047747. Epub 2015 May 29. PMID: 25942606.
115. Williamson OD, Sagman D, Bruins RH, Boulay LJ, Schacht A. Antidepressants in the treatment for chronic low back pain: questioning the validity of meta-analyses. Pain Pract. 2014;14:E33–41.
116. Moore RA, Wiffen PJ, Derry S, Toelle T, Rice AS. Gabapentin for chronic neuropathic pain and fibromyalgia in adults. Cochrane Database Syst Rev. 2014;(4):CD007938.
117. Atkinson JH, Slater MA, Capparelli EV, et al. A randomized controlled trial of gabapentin for chronic low back pain with and without a radicula component. Pain. 2016;157:1499–507.
118. Atkinson JH, Slater MA, Capparelli EV, et al. A randomized controlled trial of gabapentin for chronic low back pain with and without a radicular component. Pain. 2016;157:1499–507.
119. U.S. Food and Drug Administration . Silver Spring (MD): U.S. Food and Drug Administration; 2014. FDA drug safety communication: FDA requires label changes to warn of rare but serious neurologic problems after epidural corticosteroid injections for pain [Internet] [cited 2016 Apr 10]. Available from: http://www.fda.gov/Drugs/DrugSafety/ucm394280.htm.
120. Chan CW, Peng P. Failed back surgery syndrome. Pain Med. 2011;12:577–606.
121. Jackson CP Brown MD. Is there a role for exercise in the treatment of patients with low back pain? Clin Orthop Relat Res 1983;179:39–45.
122. Machado LA de Souza MS Ferreira PH Ferriera ML. The McKenzie method for low back pain: A systematic review of the literature with a meta-analysis approach. Spine 2006;31:E254–62.
123. Hayden JA, van Tulder MW, Tomlinson G. Systematic review: strategies for using exercise therapy to improve outcomes in chronic low back pain. Ann Intern Med. 2005 May 3;142(9):776-85. doi: 10.7326/0003-4819-142-9-200505030-00014. PMID: 15867410.
124. Akuthota V Ferreiro A Moore T Fredericson M. Core stability exercise principles. Curr Sports Med Rep 2008;7:39–44.
125. Hayden JA, van Tulder MW, Malmivaara A, Koes BW. Exercise therapy for treatment of non-specific low back pain. Cochrane Database Syst Rev. 2005 Jul 20;(3):CD000335. doi: 10.1002/14651858.CD000335.pub2. PMID: 16034851.
126. Clare HA, Adams R, Maher CG. A systematic review of efficacy of McKenzie therapy for spinal pain. Aust J Physiother. 2004;50(4):209-16. doi: 10.1016/s0004-9514(14)60110-0. PMID: 15574109.
127. Busanich BM, Verscheure SD. Does McKenzie therapy improve outcomes for back pain? J Athl Train. 2006 Jan-Mar;41(1):117-9. PMID: 16619104; PMCID: PMC1421491.
128. McCracken LM Turk DC. Behavioral and cognitive–behavioral treatment for chronic pain. Outcome, predictors of outcome, and treatment process. Spine 2002;27:2564–73.
129. Turner JA. Educational and behavioral interventions for back pain in primary care. Spine 1996;21:2851–9.
130. van Tulder MW Koes BW Bouter LM. Conservative treatment of acute and chronic nonspecific low back pain: A systematic review of randomized controlled trials of the most common interventions. Spine 1997;22:2128–56.
131. Morley S Eccleston C Williams A. Systemic review and meta-analysis of randomized controlled trials of cognitive behaviour therapy and behaviour therapy for chronic pain in adults, excluding headache. Pain 1999;80:1–13.
132. Hoffman BM Papas RK Chatkoff DK Kerns RD. Meta-analysis of psychological interventions for chronic low back pain. Health Psychol 2007;26:1–9.
133. Ostelo RW van Tulder MW Vlaeyen JW et al.  Behavioral treatment for chronic low-back pain. Cochrane Database Syst Rev 2005;1:CD002014.