Disentangling the lumbar PiVD Puzzle: a narratiVe reView

Lumbar prolapse intervertebral disc (PIVD) is a common back related disability throughout the world. It is one of common cause for work absenteeism and pose high economic burden on society. Till date, the etiology of lumbar PIVD has not been clearly established. Mechanical compression and chemical irritation are the major pathophysiological changes in lumbar PIVD. The accurate diagnosis of lumbar PIVD is a prerequisite for appropriate therapy. Lumbar PIVD results in significant disability and loss of productivity. Therefore, it is pertinent to summarize the intricacies and nuances of Lumbar PIVD as well as its evidence based management. Various cost effective and time saving protocols are available in surgical and non-surgical management of lumbar PIVD. In the present review, an attempt has been made to highlight etiology, underlying pathophysiological mechanisms of lumbar PIVD, as well as evidence based management of lumbar PIVD.

Patient may need to undergo surgery. Failure of conservative treatment and progressive neurological deficit or cauda equina syndrome are indications of Surgery [5].

ANAtOMY OF tHE INtErVErtEbrAL DIsc
Disc is made of three components: cartilaginous endplates, annulus fibrosus (AF), and nucleus pulposus (NP). Peripheral part of disc is annulus fibrosus while nucleus pulposus is the central one.
The cartilaginous end plates are located on bodies of adjacent vertebra. The annulus fibrosus has a unique multilayer structure made up of collagen type I, type II fibers and proteoglycans, each layer oriented at 30° to horizontal and successive layer in opposite direction in such a way that leads to a criss-cross pattern. Such unique structure gives the annulus more tensile modulus against torsional, axial, and tensile loads [3]. Nucleus pulposus contains approximately 70% water, notochordal cells along with fibroblast and chondrocyte like cells. Noto-chordal cells stimulate collagen and proteoglycans production and control apoptosis of chondrocyte like cells [6]. Hydrostatic pressure is generated in disc due to imbibed water. Hydrophilic proteoglycan macro-molecules of nucleus pulposus make a unique composition within collagen matrix. It is encircled by annulus peripherally and end plates above and below. The nucleus pulposus provides resistance to axial compression. The endplates are composed of mainly of water followed by chondrocytes, proteoglycans (PGs), and type II collagen. Capillary network of cartilaginous layer may extend into the outer portions of annular fibrosus upto a short distance that provide nourishment to otherwise avascular disc [7]. Nutrition of disc cells occurs via diffusion through the vertebral end plates. Disc is poorly innervated. Normally, nucleus pulposus and inner annulus fibrosus has no innervations. However, outer annulus fibrosis is innervated [3].

DIsc PrOLAPsE Or HErNIAtION
As per combined statement of the North American Spine Society, the American Society of Spine Radiology, and the American Society of Neuroradiology, disc herniation can be defined as "localized or focal displacement of disc material beyond the limits of the intervertebral disc space". Almost three fourth cases of disc pathology are of degeneration and one fourth are actual disc herniation [8]. Herniated discs can be classified as "protrusion", "extrusion", or "sequestration". Protrusion is focal bulging of disc than diameter in have wider based herniations canal. In Extrusion, nucleus pulposus ruptures through annulus with a smaller base and larger herniation in the canal. In sequestration, disc has migrated away and no contact between herniated part and the remaining disc [8].

EPIDEMIOLOGY
There are a number of risk factors that may contribute to lumbar PIVD. Lumbar disc herniation is more common in males and an average age of 41 years [9]. Bostman found that in Finland, 27% of patients who underwent a lumbar disc surgery were obese, whereas at same time obesity prevalence was only 16% among population of Finland. Overweight and obese patients are more prone to lumbar radiculopathy as compared to Non-obese people [9]. Obese persons are thirty times more prone to re-operation after microdiscectomy [10]. Mobbs et al. stated that reoperation for lumbar PIVD in diabetics is more frequent as compared to non-diabetics [10]. Due to some comorbidities, impaired microcirculation of disc increases the chances of lumbar PIVD. Certain occupations may be a cause for lumbar PIVD. Most commonly affected level is L4-L5 [4]. Twisting mechanism in combination with axial load or flexion with axial load can be a biomechanics of lumbar PIVD [11]. In a retrospective study Alpesh et al. [12] support an inheritable predisposition of lumbar disc herniation [12]. Lumbar disc herniation is multifactorial, including contributions from mechanical stresses to the spine, age-dependent disc degeneration, biochemical factors and genetics.

PAtHOPHYsIOLOGY
Natural degenerative changes in intervertebral disc include decrease in number of capillaries, altered cell morphology and density of nucleus pulposus. Annular clefts and apoptosis of fibroblast-like cells are increased in intervertebral disc [13]. Disc herniation is categorized in three steps: protrusion, extrusion and sequestration ( Figure 1). Mechanical compression is commonly considered as cause of radiculopathy. Nerve roots are composed of endoneurium similar to peripheral nerve while cerebrospinal fluid and dural lining are present instead of perineurium and epineurium respectively. Such type of structure make nerve root soft and prone to get compressed mechanically. Nerve roots are in close approximation to vertebral bodies. Disc herniation exerts tensile force on nerve root similar to bowstring effect. Nutrition is impaired in mechanically compressed nerve root as both blood flow and nutrient diffusion are compromised. Intraneural edema, nerve fibrosis and injury may lead to compartment syndrome in mechanically compressed nerve. A large number of studies conclude that mechanical effect is main contributing factor in radiculopathy, while some studies claims that chemical irritation along with mechanical compression are responsible for radiculopathy in lumbar PIVD [14]. Disc herniation can be seen in magnetic resonance imaging ( Figure 2). On the basis of magnetic resonance imaging, it can be in-ferred that compression of nerve root is mostly asymptomatic. According to a study, 20% of asymptomatic participants of age below 60 years and 36% of participants of age above 60 years have radiological evidences of disc herniation. It is claimed that irritated nerve root are more prone to mechanical compression as compared to normal nerve roots [14]. Some bioactive molecules found in nucleus pulposus like interleukins, tumor necrosis factor-(TNF) alpha and some other factors are responsible for nerve root sensitization making it prone to mechanical compression [15]. TNF-alpha can be the factor responsible for decrease in nerve conduction velocity. The pathophysiology of lumbar disc herniation has been summarized in Figure 3.

cLINIcAL PrEsENtAtION
Radiating pain, abnormal sensation and weakness in area of lumbosacral nerve roots in lower limb are primary clinical presentations of lumbar disc herniation [16]. There may be localized paresis, coldness in leg, limited trunk flexion, exacerbation in pain with sneezing, straining and coughing [16]. Patients complain difficulty in sitting, as it increases disc pressure upto 40% as compared to upright standing [17]. Forward flexion also contributes to increase in pain as the pressure on lumbar disc is increased by 100-400% [17]. So lumbar disc prolapse induces radiating pain, abnormal sensation, weakness, paresis, cold leg, limited range of motion and difficulty in sitting.

DIAGNOstIc GUIDELINEs
Initial screening for diagnosis can be done by straight leg raise (SLR) test along with Hancock rule [18,19]. Three symptoms should be positive out of following four: pain along dermatome, abnormal reflex, motor weakness and sensory deficits [18]. Importance and validity of negative SLR test in clinical diagnosis is supported by a number of studies, irrespective of level of involvement [20][21][22]. Importance of crossed SLR tests for clinical diagnosis is also supported by a number of studies [20][21][22]. Various imaging tools are used to confirm the diagnosis.

radiographic imaging
Radiograph is an important tool used to screen patients for diagnosis. Flexion and extension views may also be helpful along with antero-posterior (AP) and lateral views. Radiographs show compensatory scoliosis, osteophytes and reduced intervertebral space in lumbar disc prolapse.

Magnetic resonance imaging
Magnetic resonance imaging (MRI) is used as a gold standard tool for confirmation of lumbar disc prolapse due to its high inter-observer reliability and 97% accuracy [23].

computed tomography scan
Computed tomography scan (CT-Scan) is also an important diagnostic tool. Clinical importance of CT-Scan is supported by a number of studies [24]. It can be used as alternative tool to MRI for suspected cases.

trEAtMENt
Characteristics of major included studies are summarized in Table1. Treatment is broadly classified into operative and non-operative management. Non-operative management is further sub classified as pharmacological and non-pharmacological management.

Non-operative management
Non-operative management for lumbar disc prolapse is first choice of treatment in majority of cases. Conservative and surgical procedures both are equally effective outcomes at midterm and long term [25]. Conservative management for lumbar disc prolapse consists of non-steroidal anti-inflammatory drugs (NSAIDs), steroids, acupuncture, core exercise, taping, ergonomic advise and Physiotherapy [26][27][28][29]. Non-steroidal anti-inflammatory drugs and pregabalin are most commonly used agents and have different clinical impact [30]. A variety of lumbar epidural injections are used clinically [31][32][33][34][35][36]. However, effectiveness of such injections varies from 20-95% decrease in pain on long term follow up. Trans-foraminal injections give better result than caudal or interlaminar technique [36]. Position of patient during epidural injection can also affect the success of treatment. Decubitus position during epidural injection gives better outcome at 6 month and 12 month as compared to prone position [37]. Outcomes of epidural injections can be predicted by radiologic evaluation [38]. Epidural and subcutaneous injection of TNF-α inhibitors are effective in clinical improvement [39]. Visual analog scale(VAS) Caudal epidural steroid injection is safe and better to decrease pain and disability than selective nerve root block(SNRB) in prolapsed lumbar intervertebral disc. Shin et al. concluded the combined effect of multiple therapies including acupuncture, bee-venom pharmacopuncture, herbal supplementation and spinal manipulation are effective in long term to improve VAS as well as ODI score [40]. Spontaneous resorption is also possible [41]. Traction and spinal decompression is also effective in decreasing disability and VAS score [42][43][44][45]. Joint mobilization, core training and active exercises are effective in improving recovery outcomes in lumbar disc prolapse [46][47][48]. Mesenchymal stem cell (MSC) therapy and platelet rich plasma (PRP) injection are also used clinically nowadays. Studies corroborate clinical improvement in ODI and VAS score without any complications [49][50][51][52].

Operative treatment
Surgical management is beneficial in short term as compared to non-operative management. However, in mid to long term both have no significant differences [25].

Minimal invasive surgery
Such type of intervention leads to less soft tissue lesion, reduced hospital stay and early joining back to work [53]. Trans-foraminal, trans-iliac, inter-laminar and posterolateral are few percutaneous endoscopic minimal invasive approach used commonly for spine surgery [54][55][56]. These interventions are associated with reduced blood loss, re-operation rate, operative time and other complications as compared to open procedure [57].

Other surgical procedure
Discectomy, instrumental posterior lumbar interbody fusion, dynamic stabilization with nucle-otomy and plasma disc decompression are used having significant results [58,59]. Previously discectomy was used as a gold standard surgical procedure in lumbar disc prolapse. Discectomy procedure has a number of complications like dural tear, postoperative infection; nerve root injury and increased hospital stay [60][61][62]. Recent meta-analysis shows advantages of microdiscectomy over open discectomy, such as shorter hospital stay and reducing initial post-operative pain. Rongqing et al. [63] stated that percutaneous endoscopic lumbar discectomy showed shorter hospital stay and time of return to work [63].

cONcLUsIONs
Lumbar disc is almost avascular. It has small regenerative ability and bears significant axial load. Multidirectional movements along with rotational forces and axial loads commonly lead to lumbar disc herniations that may be associated with radiculopathy. Proper and accurate diagnosis for assessment of level involved, severity of compression and neurological involvement can be assessed by clinical examination, patient history assisted by radiological evidences of magnetic resonance imaging (MRI) and computed tomography scanning (CT-scan) etc. There are number of interventions including conservative and surgical approaches that are used for management of lumbar PIVD. Authors opine that for an effective and evidence based practice, attention of the therapist should be focused on the biomechanics of lumbar PIVD and specific biochemical factors that leads to pain, disability and other associated complications due to lumbar PIVD.