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Pathology/pathogenesis of lumbar disc degeneration
 

Pathology/pathogenesis of lumbar disc degeneration

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Pathology/pathogenesis of lumbar disc degeneration

Pathology/pathogenesis of lumbar disc degeneration

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    Pathology/pathogenesis of lumbar disc degeneration Pathology/pathogenesis of lumbar disc degeneration Document Transcript

    • INDEX  BASIC DISC ANATOMY & PHYSIOLOGY  NORMAL DISC AGING  DISC / VERTEBRAL COLUMN PATHOLOGICAL CHANGES IN DEGENERATIVE DISC DISEASES  THE VASCULAR BASIS FOR DISC DEGENERATION BASIC DISC ANATOMY & PHYSIOLOGY The intervertebral discs may be thought of as soft tough pads that separate the bones (vertebrae) of the spine from one another. Their basis function is three-fold: 1) they act as a ligament by holding the vertebrae of the spine together, 2) they act as a shock absorber which carries the downward weight of the body (axial load) while in an up right position, and 3) they act as pivot point, which allows the spine to bend and twist. www.yassermetwally.com Professor Yasser Metwally www.yassermetwally.com
    • There are 23 discs in the human spine: 6 in the neck (cervical region), 12 in the middle back (thoracic region), and 5 in the lower back (lumbar region). We shall focus on the lumbar discs on this page. Figure 1 Depicts a Front view (AP) of the lumbar spine. Here we can see how the discs (blue) lie in between every vertebrae. Spinal nerves (yellow) have emerged from between every two vertebrae and travel down the lower limbs to innervate (give life to) the skin and muscle. Note how the sciatica nerve is formed within the pelvis by branches from the last three lumbar spinal nerves. It is this giant nerve that causes so much trouble in many of us chronic pain sufferers. The disc is made up of three basic structures: the nucleus pulposus, the annulus fibrosus, and the vertebral end-plates. Although their composition percentage differs, the latter three structures are made of three basic components: proteoglycan (protein), collagen (cartilage), and water. We will learn all about these structures below. www.yassermetwally.com Professor Yasser Metwally www.yassermetwally.com
    • Figure 2. Shows a cut-away posterior view of the lumbar spine. Now we can better visualize how the sciatic nerve is formed and see just how close the spinal nerve roots come to the intervertebral disc. Any herniation of the posterior disc may compress the spinal nerve root and result in severe lower back pain and lower limb pain (sciatica).  Axial Disc Anatomy and physiology: The Nucleus Pulposus is the water rich gelatinous center of the disc which is under very high pressure when the human is up-right. It has two main functions, to bear or carry the downward weight (axial load) of the body, and to act as a 'pivot point' from which all movement of the lower trunk occurs. It's third function is to act as a ligament and bind the vertebrae together. The annulus Fibrosus is a much more fibrous structure that the nucleus pulposus. It has a higher collagen content and lower water content. Its job is to 'corral' the pressurized nucleus and keep it from exploding outward. It is made of 15 to 25 concentric sheets of collagen, (a cartilage like substance) called the Lamellae. The lamellae are arranged in a special configuration which makes them extremely strong and easily able to contain that pressurized nucleus pulposus. The spinal nerves roots and Spinal Nerves are extensions of the brain and spinal cord. Like super highways the spinal nerves and nerve roots are constantly carrying electric messages to and from the brain. The nerve roots exit the spine through bony holes called the Intervertebral Foramen (IVF). As the nerve roots 'peal-off' from the cauda equina, one sensory nerve root and one motor nerve root, and head for their respective IVF. Note worthy is the fact that our two nerve root pass very close to the back of the disc. Once within the IVF the two nerve roots merge into one spinal nerve. The spinal nerves are called 'mixed nerves' for they contains both sensory nerve fiber (afferent) and motor nerve fiber (efferent). After leaving the spine through the IVF, the nerve split into a posterior www.yassermetwally.com Professor Yasser Metwally www.yassermetwally.com
    • division (Dorsal Ramus) and an anterior division (Ventral Ramus). The Dorsal Ramus connect to the muscle and skin over the lower back and butt and the Facet Joint. The Ventral Ramus combine in the pelvis and form the giant Sciatic Nerve and Lateral Femoral Cutaneous Nerve which connect to all the skin and muscle of the lower limbs. The ventral ramus has a 'recurrent branch' that connects to the back of the disc, as well as the sympathetic nervous system (Grey Ramus Communicans); this special nerve is called the Sinuvertebral nerve (SN) (see below). In the lumbar spine (below the L1 disc level) there is no spinal cord. Instead the nerve roots hang in an enclosed sac which is called the Thecal Sac. The thecal sac, which protects the dangling nerve roots, is made up of two distinct but tightly bound layers called the dura mater and arachnoid mater. A clear fluid called Cerebral Spinal Fluid is also found within the thecal sac. This fluid protects the nerve roots and also supplies nutrients. Note how the nerve roots, that collectively are called the Cauda Equina, are highly organized within the thecal sac. Because of this arrangement, which always puts the lower level nerve root in front, it is possible for a large compressive L4 disc herniation to irritate the S1 and/or L5 roots. This may explain why disc herniations do not always match their dermatomal distribution - i.e., a disc herniation at L4 may clinically present as nerve root pain (radicular pain, sciatica) and dysfunction in the S1 and/or L5 distributions! The Epidural Space is the space between the bony neural canal and the thecal sac, or the space 'outside' of the thecal sac. Unlike my drawing this space is filled with blood vessels and fat. Note worthy is the fact that this is the region where 'epidural steroid injections' are placed. The Facet Joints zygapophyseal joints) of the spine are where the vertebrae articulate (join) with each other. Actually, the gap between the inferior and superior articular processes is the true facet joint (white region). Collectively the inferior and superior articular processes and the facet joint are called the zygapophyseal Joints or articular pillars. These joints help carry the axial load of the body and limit the range of motion of the spine. They also make up the back of the intervertebral foramen and may cause stenosis if they hypertrophy in later life (lateral stenosis). The Ring Apophysis is the 'naked bone' of the outer periphery of the vertebral bodies. The very outer fibers of the disc (Sharpey's Fibers) anchor themselves into this region. Bone spurs (Osteophytes) may arise from the ring apophysis as the result of the later stages of Degenerative Disc Disease (DDD) and/or Osteoarthritis (Spondylosis). Specifically, osteophytes arise from the prolonged 'pulling and tugging' of 'Sharpey's Fibers' at their anchor points. The Posterior Longitudinal Ligament (PLL) is a strong ligamentous tissue which courses down the anterior aspect of the vertebral canal and is attached to the outer fibers of the annulus fibrosus. This highly innervated (supplied with pain carrying nerve fiber) tissue is the last line-of-defense the posterior neural tissue has against the irritating and inflammatory effects of nucleus pulposus. www.yassermetwally.com Professor Yasser Metwally www.yassermetwally.com
    • Figure 3. The Sinuvertebral Nerve  The Sinuvertebral Nerve The Sinuvertebral Nerves (SN), is a mixed nerve as well. It carries both autonomic fiber (sympathetic) and sensory (afferent) fiber. The sensory portion, which has the capability to carry the feeling of PAIN, arises from the outer 1/3 of the posterior annulus fibrosus (yellow balls, fig. 3) and Posterior Longitudinal Ligament. It then spilts and attaches to both the dorsal ramus and the grey ramus communicans, although this nerves anatomy and course seems to be quite anomalous. Of importance is the fact that if irritated, the nerve ending within the disc have the potential to generate both back pain and/or lower limb pain (discogenic pain). o Discogenic Sciatica (referred discogenic pain) It is believed that the sinuvertebral nerve-endings are 'sensitive' to the irritating effects of degenerated nucleus pulposus, that may be leak into the outer region of the annulus from a grade three annular tear. Amazingly, the sinuvertebral nerve also innervates (connects to) the disc above and below! So, the sinuvertebral nerve of the L4 disc also innervates the L5 and L3 disc. This may help explain why a L4 disc herniation/annular tear may clinically present with some signs of L5 and/or L3 involvement as well. It also carries autonomic nerve fiber to the blood vessels (not shown in fig. 3) of the epidural space. Sympathetic nerves control how the blood vessels function (vasomotor & vasosensory). Although rare, www.yassermetwally.com Professor Yasser Metwally www.yassermetwally.com
    • injury to these sympathetic nerves may cause RSD symptoms in the patients lower limbs; this usually would occur following surgery. The exact pain-pathway (how pain travels from the disc to the spinal cord) of discogenic pain is another fascinating and controversial subject. It seems that the sensory pathway from the sinuvertebral nerves into the spinal cord, does not take the 'expected' route in every patient. Some research has demonstrated that pain-signals travel from the disc, re- enter the IVF (via sinuvertebral nerve) and Dorsal Root Ganglion at the same level. Other, more recent research has indicated that pain-signals travel from the disc, through the sinuvertebral nerve, through the Gray Rami Communicans, into the Sympathetic Trunk (ST), up the sympathetic chain to the L2 vertebral level, through the gray rami communicans, into the L2 dorsal rami, into the L2 IVF, and into the L2 Dorsal Root Ganglion. The latter pain pathway is why some investigators believe that lower level disc herniations may present as L2 dermatomal pain (groin region) in some patients! Figure 4. A sagittal view (lateral view) of the 'motion segment'; Two vertebrae which are 'sandwiching' the intervertebral disc. The disc (which is made of a annulus fibrosis and the nucleus pulposus) is made up of three distinct areas: 1) The nucleus pulposus (green, fig 4), which is a water rich (due to proteoglycan aggrecan & aggrecate molecules which trap and hold water within the disc) gel in the center of the disc; 2) The annulus fibrosis (blue, fig 4), which is the fibrous outer portions of the disc that is made up of type I collagen; and 3) The vertebral end-plates (yellow, fig 4), which are cartilaginous plates that attach the discs to the vertebrae and supply food (nutrients) to the inner 2/3 of the annulus and entire nucleus pulposus. To further increase the strength of the annulus fibrosus, individual sheets of collagen are layered throughout the annulus. There sheets of collagen are called lamellae (black curved lines within blue, fig 4). The very outer lamellae (Sharpey's fibers), unlike the inner lamellae, are anchored into the solid bony periphery (Ring Apophysis) of each vertebral body. This is the region that 'osteophytes' or bone spurs typically like to form. www.yassermetwally.com Professor Yasser Metwally www.yassermetwally.com
    • CT SCAN / MRI ANATOMY, CLINICAL CORRELATION Figure 5. MR study of lumbar disc 5. Although this patient does have a moderate degree of disc degeneration (black disc) and a small non-compressive 4 millimeter central disc herniation, he had a very large 'central canal' which nicely demonstrates the axial MRI anatomy. The nucleus pulposus is not visible on these images. One reason for this is because the disc has too much desiccation to distinguish between the annulus and nucleus, and the other reason is that this is a T1 Weighted image which will not differentiate between the high water content of the nucleus and the more arid annulus; however, on a normal, non-degenerated disc, you can easily see a nuclear region and an annular region on the T2 Weighted image. The 'posterior neural structures' include the Traversing Nerve Roots, the Thecal Sac (dura and arachnoid mater) and the exiting nerve roots that lie within the IVF (pink zone) and not very visible on this particular image. www.yassermetwally.com Professor Yasser Metwally www.yassermetwally.com
    • Figure 6. Demonstrates another axial view of a normal health L4 disc. Now we can see a distinct nuclear region and annular region. Note the Facet Joints (pink star on one of them) are imaged 'white' as well. Again this indicates a high fluid content; in this case it's the synovial fluid of the facet joint that is cause the increased signal. Figure 7. CT myelography of the lumbar region. BLUE: This is the 'Central Region' and is located directly behind the disc and encompasses the anterior aspect of the thecal sac. Since www.yassermetwally.com Professor Yasser Metwally www.yassermetwally.com
    • the PLL (posterior longitudinal ligament) is at its thickest in this region, the disc usually herniates slightly to the left or right of this central zone. PINK: This is the 'Paracentral Region' or 'Lateral Recess' and is located just outside of the Central Region. Because the PLL is not as thick in this region, disc herniations are frequently found here; in fact, this is the number one region for disc herniations to occur in. The Traversing Nerve Roots, which are the neural structures found in this zone, are frequently contacted, deviated and compressed in this zone. GREEN: This is the 'Intraforaminal Zone', also known as the 'Subarticular Zone', and is located within the intervertebral foramen (IVF). It is fairly rare for a disc to herniate into this region or beyond; in fact, only 5% to 10% of all disc herniation occur here or farther out. When herniations do occur in this zone, they are often very troublesome for the patient. This is because a super-delicate neural structure called the 'Dorsal Root Ganglion' (DRG) lives in this zone. Any compression of the DRG can result in severe pain, sciatica ( radiculopathy) and nerve cell body (neuron) damage. YELLOW: This is the 'extraforaminal zone' and, as the name implies, is just outside (lateral to) of the IVF. Again, it is very rare for a disc to herniate into this region, but when it does happen, it is often very troublesome for the patient and surgeon. A herniation in this zone may also irritate the 'Sympathetic Nervous System' and cause RSD like symptoms in the lower limb. www.yassermetwally.com Professor Yasser Metwally www.yassermetwally.com
    • Figure 8. CT myelography. Normal structure at L5 vertebra DISC PHYSIOLOGY The normal human intervertebral disc, which is considered the largest avascular structure in the human body, is made up of two main components, proteoglycan and collagen (type I and type II). The annulus is mostly made of collagen, which is a tough fibrous tissue similar to the cartilage that is found in the knee, and the nucleus is made mostly of proteoglycan. Proteoglycans, which are produced by disc cells that resemble chondrocytes, are extremely important for disc function and are what 'trap' and hold water molecules (H20) within the tissue of the disc. In fact both the disc and annulus are comprised mainly of water, i.e., the nucleus is 80% water, and the annulus is 65% water. Proteoglycans are the building blocks of the aggrecan molecule which is the true 'water trap' of the disc. Aggrecans combine within the disc on strands of hyaluronan acid to form huge structures called 'Aggregates'. These super water-filled proteoglycan aggregates are what give the healthy young disc its amazing strengths and pliability, in fact a well hydrated disc is often even stronger than the bony vertebral body. www.yassermetwally.com Professor Yasser Metwally www.yassermetwally.com
    • Figure 9. Here we have the healthy disc of a teenager (cadaver). The water content is extremely high as you can even see by the 'glistening' appearance of the nucleus (which is the gray center of the white disc).  Disc Function In order for a disc to function properly, it must have high water content; this is especially true of the nucleus. A well hydrated (with water) disc is both strong and pliable. The nucleus pulposus needs to be strong and well hydrated to do its job (axial load), for it is this structure that supports or carries the lion's share of the axial load (downward weight of body) of the body. With an undamaged annulus, strongly corralling a fully hydrated nucleus, the disc can easily support even the heaviest of bodies! As the disc dehydrates (loses water) the disc loose ability to support the axial load of the body (loses hydrostatic pressure); this causes a weight bearing shift' from the nucleus, outward, onto the annulus, outer vertebral body, and zygapophyseal joints (facets). Now, we have an 'over-load' on the annulus (which may trigger other destructive biochemical reactions) which, if severe and/or is imposed upon a genetically inferior annulus, will result in pathological degenerative disc disease (spondylosis). Hydration also is important with respect to disc nutrition. As we have already mentioned, nutrients (which all living tissue needs in order to survive) must diffuse (soak) through the discal tissue in order to reach the hungry disc cells. This diffusion process is much faster and easier if the diffusing tissue has a high water content. We may use 'swimming' as an analogy: It's easier to swim through the water, than through the sands of a desert. The sands of the desert would be a dehydrated disc, and the water would be a hydrated disc. So, water and disc hydration are one of the key factors for a normally functioning spine and well fed disc. www.yassermetwally.com Professor Yasser Metwally www.yassermetwally.com
    •  Proteoglycans, which are produced by disc cells that resemble chondrocytes, are extremely important for disc function and are what 'trap' and hold water molecules (H20) within the tissue of the disc. In fact both the disc and annulus are comprised mainly of water, i.e., the nucleus is 80% water, and the annulus is 65% water. Proteoglycans are the building blocks of the aggrecan molecule which is the true 'water trap' of the disc. Aggrecans combine within the disc on strands of hyaluronan acid to form huge structures called 'Aggregates'. These super water-filled proteoglycan aggregates are what give the healthy young disc its amazing strengths and pliability.  Water is held within the disc by tiny sponge-like molecules called proteoglycan aggrecans. These 'super sponges' have an amazing ability to attract and hold water molecules, and can in fact hold over 500 times their own weight in water; this gives the non-dehydrated disc the tremendous 'hydrostatic pressure' which is needed to bear the axial load of the body. o Disc hydration Water is held within the disc by tiny sponge-like molecules called proteoglycan aggrecans. These 'super sponges' have an amazing ability to attract and hold water molecules, and can in fact hold over 500 times their own weight in water; this gives the non-dehydrated disc the tremendous 'hydrostatic pressure' which is needed to bear the axial load of the body. Amazingly, the aggrecans water absorption is so powerful that over night (non-axial loading) the height of the disc and the body will actually measurably increase due to the discs engorgement with water. This phenomenon is called 'Diurnal Change' and is only present in non-degenerated discs. Disc cells, particularly the chondrocyte-like cells of the nucleus and inner annulus, manufacture proteoglycan aggrecan molecules. Like little factories, they create, replace and rebuild aggrecan molecules. As long as the disc cells have food (glucose), building material (amino acids) and oxygen all is well in disc-land. It is also important for them to have a non-acidic working environment, which is taken care of, since wastes are diffused out of the disc through the same way nutrients diffuse in. In the living disc up to 100 aggrecans combine on a long piece of 'hyaluronan acid' to form giant proteoglycan aggregate molecules. It's these aggregates that are found within the disc in the real world. The nucleus pulposus has a unique ability to bind water. Initially the water binding capacity of the nucleus was attributed to fluid exchange governed by osmotic pressure. The cartilaginous end-plates were thought to act as a semipermeable membranes with the nucleus drawing water from the vertebral bodies. It is presently thought that the hydrodynamics of the disc depend upon the nucleus possessing the properties of a gel rather than upon osmosis. this gel contains some cartilaginous cells, fibroblasts, collagen framework and the ground substance which is mostly mucopolysaccharides with varying amount of salt and water. The high imbibition pressure is produced by the mucopolysaccharides contained within the gel which can bind almost nine times its volume of water. The water content of the nucleus is not chemically bonded and can be expressed from the nucleus by prolonged mechanical pressure. www.yassermetwally.com Professor Yasser Metwally www.yassermetwally.com
    • Box 1 Factors necessary for chondrocytes-like disc cells to manufacture proteoglycan aggrecan molecules  Glucose  Building material (amino acid)  Oxygen  Non-acidic environment  Disc Nutrition The intervertebral disc is the largest avascular structure in the human body. The reason for this is because it has no direct blood supply like most other body tissue. Nutrients for the disc are found within tiny capillary beds (black arrows, fig. 6) that are located in the subchondral bone, just above the vertebral end-plates . This subchondral vascular network 'feeds' the disc cells of the nucleus and inner annulus through the diffusion process. Figure (fig. 10) shows the 'disc feeding vascular system' . Note that the outer annulus has its own blood supply that is embedded within the very outer annulus. For the outer annulus this is a much more efficient system and nutrients don't have to diffuse very far to find their disc cells. The 'more direct' blood supply of the outer annulus is why tears of the outer 1/3 of the annulus will heal with the passage of time, which unfortunately is not true for tears of the rest of the disc. Research has indicated that disc tears will not heal in the inner zones of the disc - probably because of the avascular nature of the inner two thirds of the disc. Note the nutrients (pink balls, fig. 10)) diffuse directly into the tissue of the outer annulus, where as the nucleus and inner annulus has a much longer diffusion route that is might be blocked by the vertebral end-plates if calcified. Note how the nutrients (pink balls) are released from the blood vessels (red, fig. 10) in the subchondral bone just under the vertebral end-plates. These nutrients must 'diffuse' or soak their way through the vertebral end-plates and into the disc. This 'diffusion method' is how the cells of the disc get the nutrients oxygen, glucose, and amino acids which are required for normal disc function and repair. This poor blood/nutrient supply system to the disc is one of the main reasons that the disc ages and degenerates so early in life. Nutrients for the disc are found within tiny capillary beds that are located in the subchondral bone, just above the vertebral end- plates. This subchondral vascular network 'feeds' the disc cells of the nucleus and inner annulus through the diffusion process. www.yassermetwally.com Professor Yasser Metwally www.yassermetwally.com
    • Figure 10. Disc anatomy, disc vascular system and disc nutrition The 'diffusion feeding process' is enhanced somewhat by a phenomena called 'Diurnal Change'. Our discs have the ability to expand and compress over the course of a day. As we start the day our discs, like squeezing out a sponge, will compress and dehydrate because of the gravity and physical activity which place axial loads upon the discs. In fact a healthy disc will shrink down some 20%, which in turn decreases our height by 15 to 25mm. As we sleep and decompress our spines, our discs swell with water plus nutrients and expand back to their fully hydrated state. This tide-like movement of fluids in and out of the disc will help with the movement of nutrients into the avascular center of the disc.  Advanced Anatomy & Physiology o The Nucleus Pulposus The nucleus pulposus is a hydrated gelatinous structure located in the center of each intervertebral disc that has the consistency of toothpaste. Its main make-up is water (80%). Its solid/dry component make-up are proteoglycan (65%), type II collagen fiber (17%) and a small amount of elastin fibers. Collectively the proteoglycans and the collagen are called the 'nuclear matrix'. The cells of the disc, which produce the water holding proteoglycan molecules are very similar to chondrocytes seen in articular cartilage and are also held within the matrix. www.yassermetwally.com Professor Yasser Metwally www.yassermetwally.com
    • Proteoglycans are found in several structural forms within the disc but the most important 'arrangement' is called a proteoglycan aggrecan. These aggrecans main function is to trap and hold water, which is what gives the nucleus its strength and resiliency. Like a 'super sponge', aggrecans can trap and hold over 500 times their weight in water! The nucleus has two functions. The first is to bear most of the tremendous axial load coming from the weight of the body above and second to 'stand-up' the lamellae of the annulus - so that the annulus can reach its full weight baring potential. In order for proper weight bearing the nucleus and the annulus must work hand in hand. o The annulus Fibrosis The annulus is the outer portion of the disc that surrounds the nucleus. It is made up of 15 to 25 collagen sheets which are called the 'lamellae'. The lamellae are 'glued' together with a proteoglycans. These sheets encircle the disc and, in concert with the nucleus, give the disc tremendous axial load strength. Figure 11. A, The annulus Fibrosis. B, The 'Nucleus Pulposus' (pink), which is a water-rich gel-like mass of proteoglycan material, has the duty to support the tremendous 'Axial- Load' (weight) of the body. This nucleus is 'corralled' by the stronger 'annulus Fibrosus'. The annulus is made out of concentric rings of a cartilage-like material called 'lamellae'. It is this specially arranged collagen that gives the annulus the tremendous strength needed to hold that nucleus in place. www.yassermetwally.com Professor Yasser Metwally www.yassermetwally.com
    • The posterior portion of the annulus if further strengthened by the 'posterior longitudinal ligament'. This structure is the final barrier between the disc and the delicate spinal cord, and nerve roots. The biochemical make up of the annulus is similar to that of the nucleus with different proportions. The annulus is 65% water, with the collagen, both type I and II making up 55% of the dry weight, and proteoglycans (mostly the larger aggregate type - 60%) making up 20% of the dry weight. 10% of the annulus also contain 'elastic fiber' that are seen near where the annulus attaches into the vertebral end-plate. The lamellae are made up of both Type I (very strong type) and Type II collagen fiber. The very outer lamellae are almost all Type I. As we move inward toward the nucleus the more Type II is seen and less Type I. The very inner layers are very hard to distinguish from the nucleus. There is not a clear boundary between the nucleus and the annulus. A simply amazing fact about the lamellae design is that the collagen fibers that make-up each lamellae run parallel at a 65 degree angle to the sagittal plane. Even more amazing is the fact that the each lamellae are flipped so that the 65 degree angle alternates between every lamellae, one to the right then one to the left. This design greatly increases the shear strength of the annulus and makes it stronger for cracks to develop through the layers of the annulus. The function of the annulus is to help the nucleus support the axial weight from the body. The annulus does need some help from the nucleus in order to achieve its strongest configuration. It relies on the nucleus to push it outward which keeps the lamellae from collapsing inward. The nucleus must keep a very high hydrostatic pressure to achieve this. Box 2. Function of the proteoglycan 1. Proteoglycan traps water. Water is held within the disc by tiny sponge-like molecules called proteoglycan aggrecans. These 'super sponges' have an amazing ability to attract and hold water molecules, and can in fact hold over 500 times their own weight in water; this gives the non-dehydrated disc the tremendous 'hydrostatic pressure' which is needed to bear the axial load of the body. 2. The lamellae of the annulus fibrosus are glued together by proteoglycan o The Vertebral End-Plates Both the top and the bottom of each vertebrae (spinal bones) are capped with a thin ¾ millimeter cartilaginous pad called the 'Vertebral End-Plate'. Despite their name, these end-plates are not attached to the subchondral bone of the vertebrae but are instead strongly interwoven into the annulus of the disc. It is for this reason, as well as strong morphological similarities, that the vertebral end-plates are considered part of the disc and not part of the vertebral body. www.yassermetwally.com Professor Yasser Metwally www.yassermetwally.com
    • Figure 12. The Vertebral End-Plates The biochemical morphology of the end-plates is extremely similar to that of the disc: Water, proteoglycans, collagen and cartilage cells (chondrocytes). The concentration scheme of these components also mirrors that of the disc: The center of the end-plate is mostly water and proteoglycan. As we move outward toward the periphery, more and more collagen is seen with less and less proteoglycans. This similar biochemical makeup and distribution scheme helps the diffusion of nutrients between the subchondral bone of the vertebra and the depths of the disc. The very outer rim of the vertebrae is not covered by the end-plate, which leaves a ring of exposed bone on the periphery of the top and bottom of each vertebra. This exposed peripheral area is called the 'Ring Apophysis' and is often a site for the development of spur formation associated with the degeneration process. BIOMECHANICS OF DISC DEGENERATION In the lumbar region, the compressing forces occur primarily in a vertical axis. Both the nucleus and annulus act to absorb these forces and redistribute them evenly in all direction. The nucleus bears all the vertical load and the annulus bears only the tangential load. The liquid property of the nucleus enables it to alter its shape freely under pressure. This shape altering property of the nucleus enable it to withstand stresses varying in duration and magnitude, transmitting some radially to the annulus and the rest over the entire cartilaginous end- plate. With degeneration of the disc, the gel inhibition pressure of the nucleus is impaired, marked change occurs in the transmission of forces occurring along the vertical axis of the spine. The desiccated nucleus is unable to redistribute much of the vertical load radically, causing the annulus and the facet joints to sustain much of this load. www.yassermetwally.com Professor Yasser Metwally www.yassermetwally.com
    • NORMAL DISC AGING Unlike other tissues of the body, the intervertebral disc under goes an early and often severe form of aging and degeneration . In most humans, this aging/degeneration process is slow and steady, but in some the process rapidly accelerates and may lead to catastrophic failure of the disc; which in turn may lead to chronic pain and disability. This 'accelerated' form of aging/degeneration may be called Degenerative Disc Disease (DDD), although the term is commonly and erroneously used to describe any form of disc degeneration. Figure 13. The figures to the left show the difference between the normal discs and degenerative disc disease. Note the difference between the 'normal discs' (white structures) and the 'degenerated discs' (right). This is an example of moderate to severe degenerative disc disease. The discs have both collapsed and severely dehydrated. They have also an ugly brown color from the glycation process. Research has strongly linked degenerative disc disease to back pain, and sciatica, although not in every case, for it is well known that degenerative disc disease, disc protrusion, and stenosis do occur in completely asymptomatic people, but for about 10% of the population, degenerative disc disease will result in permanent chronic pain and disability. Technically it's not the actual process of degenerative disc disease that results in pain; it's the evil 'end- phases' of the disease that have the potential to generate back pain. These end-phases include annular tears (Internal Disc Disruption or IDD); disc protrusions; nerve in-growth ; and the ultimate end-phase, stenosis. The most common and striking feature of disc aging and degeneration is the loss of the proteoglycan molecule from the nucleus of the disc. Other findings of aging include a progressive dehydration, a progressive thickening (via cross-linking, glycation and CML formation), brown pigmentation formation and increased 'brittleness' of the tissues of the disc.  The three main factors of disc aging: There are three main factors that are involved in the aging process of the disc and both of these factors are amplified because of the already poor vascular supply of the disc: 1) Idiopathic blood vessel/nutrient loss and dehydration, 2.) Non-Enzymatic Glycation, Glycosylation, 3) Free radical oxidation www.yassermetwally.com Professor Yasser Metwally www.yassermetwally.com
    • Figure 14. Here we have early disc aging. The tissue of the disc has turned brown, secondary to the glycation process, and the disc has become much 'drier. The disc seen in adolescents, for comparison sake, shows us what the disc of a teenage looks like. Note the well demarcated, wet looking, nucleus (gray center) and no ugly brown tissue 1) Idiopathic blood vessel/nutrient loss and dehydration:  Short term result For unknown reasons the nucleus of the disc losses much of its vital blood supply during the first decade of life (6). Without sufficient nutrients (which are contained in the blood) the cells of the disc begin to die and the disc (especially the nucleus) becomes depleted of water. The drop in water/proteoglycan content is one or the classic signs of disc aging. Because of this dehydration of the nucleus, there is ultimately a 'weight-bearing shift' that occurs from the nucleus onto the outer annulus, ring apophysis, and the zygapophyseal joints. This increase stress upon the preceding posterior structures may lead to further more severe forms of aging, i.e., degenerative disc disease.  Long result Under the physiology section of the 'Disc Anatomy', we have learned how important disc nutrition is in maintaining a normally functioning disc. As long as the cells of the disc receive an adequate nutrient supply (which is obtain from the diffusion of oxygen, glucose, and amino acids from capillary beds just above the end-plates, into the disc), they will manufacture the proteoglycan molecule, which combines within the disc to form the larger aggrecan and aggregate molecules. It is these aggrecan molecules that trap and hold water within the disc. A fully hydrated disc will have a very high hydrostatic pressure (osmotic pressure) which makes the nucleus pulposus (which is 80% water in a normal disc) incredibly strong and able support the lion's share of the axial load from the body. The nutrients to inner annulus and nucleus have a long way to 'diffuse' in order to reach all the disc cells. (pink balls, fig 6) Without an adequate supply of nutrients, the cells of the disc will die. If the cells of the disc failed to get proper nutrients - such as oxygen, or glucose - or if the pH level of the disc rose (because waste is not being diffused out of the disc), disc cells would die and stop producing www.yassermetwally.com Professor Yasser Metwally www.yassermetwally.com
    • the vital proteoglycan molecule; without proteoglycans, the disc losses its water content (dehydrates) and losses its hydrostatic pressure (osmotic pressure). This lost proteoglycan content is the most striking feature of disc aging and degeneration. By adulthood over 50% of the cells of the disc are dead. So what's killing the disc cells and resulting in this loss of proteoglycan content?. It seems that the human disc becomes 'nutritionally compromised' from the moment we begin to stand and walk. An idiopathic "obliteration" of portions of the nutrient-providing capillary beds, which lie just above the vertebral end- plates. (These capillary beds are the only source of nutrients for the cells of the inner annulus and nucleus) is frequently observed very early in life, amazingly, this 'auto- destruction' begins within the first two years of life, and worsens over the next 8 years and between the ages of 3 and 10 there is "a dramatic decrease of physiologic vessels in the end- plate and an abundance of areas with obliterated vessels. and a substantial increase in (disc) cell death." These findings suggest that the initial causation of disc aging and degeneration is 'nutritional compromise', secondary to an idiopathic loss of the discal blood supply above the vertebral end-plates. Other factors affecting disc nutrition via diffusion rates of nutrients through the vertebral end-plates include end-plate calcification, the effects of changes in blood flow patterns secondary to arterial stenosis, smoking, diabetes, and exposure to vibration. Box 3. Pathophysiological / biochemical steps of disc degeneration  Obliteration of portions of the nutrient-providing capillary beds, which lie just above the vertebral end- plates.  Death of the proteoglycan forming disc cells  Progressive loss of the water trapping capacity of the nucleus  Loss of disc hydration  Disc degeneration  The Vicious Cycle of Disc Aging This progressive loss of proteoglycan and dehydration begins to 'snowball' out of control. Not only because of the progressive loss of nutrients, but also because of the fact that decreased hydrostatic pressure also slows the production of proteoglycan by the disc cell. Here's what this vicious cycle looks like. As the nutrient supply within the disc drops (because of blood vessel obliteration and later end-plate mineralization), the disc cells start to die. Because there are fewer available disc cells around to make proteoglycan, there is a drop in the amount of circulating An idiopathic "obliteration" of portions of the nutrient-providing capillary beds, which lie just above the vertebral end-plates is frequently observed very early in life. www.yassermetwally.com Professor Yasser Metwally www.yassermetwally.com
    • proteoglycan aggrecan molecules. This decrease in the aggrecan molecule, (which is what holds water within the disc) results in both dehydration, and a decrease in hydrostatic pressure within the nucleus. The loss of hydrostatic pressure has two negative effects on the disc: a) it will cause a further decrease in the amount of circulating proteoglycan aggrecan molecules, for we know that disc cells need a constant hydrostatic pressure level of 3 atm to function normally. Any increase or decrease in hydrostatic pressure caused a reduction proteoglycan production, which in turn decreases hydrostatic pressure even more - hence the vicious cycle. b) Now, these biochemical changes begin to change the biomechanics of the disc: With the decrease of hydrostatic pressure the nucleus, like a deflating beach-ball, can no longer carry the full axial-load (weight) of the body. A 'shift' in the axial-load distribution begins to occur, with the periphery of the disc (outer annulus, ring apophysis, and zygapophyseal joints) taking on more and more of the load and stress. Experimentally, the annulus of a degenerated disc shows a very high 'stress-load' on the annulus and not the nucleus. We will later learn that this 'load-shift' can be greatly accelerated if the volume of the nucleus is increased by trauma-induced structural damage to either the end- plate (compression fracture) and/or tearing of the inner annulus. 2.) Non-Enzymatic Glycation: Glycosylation Glycation (Glycosylation , or non-enzymatic glycation) is a biochemical reaction which occurs when reduced sugars (like glucose) come in contact with proteins (like disc collagen) in an avascular environment. The more avascular the tissue, the more severe this reaction occurs. Since the disc is the largest avascular tissue in the body, the glycation process thrives within its substance and results in a slow but steady transformation of disc collagen into a thicker and more brittle substance. Specifically, this reaction occurs between the protein molecules within the collagen, and free floating glucose (reduced sugar). This reaction is called 'posttranslational protein modification' or Glycation. Here's how it works: In the absents of oxygen, reduced sugars start to 'rub against' (bind) the proteins within the collagen. The proteins are transformed into what is called an 'Advanced Glycation End-Product' or AGE. These converted discal collagen strands (AGEs) become much more brittle and also much more 'sticky', i.e., they love to combine with their glycated neighbors in a process called 'cross-linking'. This 'cross-linking' phenomenon makes the disc thicker, more fibrous and more susceptible to the development of degenerative disc disease. It also stains the discal tissue a distinct shade of brown as noted in figure 15,16 3) Free radical oxidation Finally, the unstable AGEs molecules are oxidize by free radicals into a much more stable structure called a CML (N- Carboxymethyl -lysine). CML formation has been found to be an excellent indication of discal aging www.yassermetwally.com Professor Yasser Metwally www.yassermetwally.com
    • Figure 15. Dessication of the nucleus pulposus associated with multiple annular tears (eg, radial, circumferential). Notice that the disc is bulging without actual herniation. Because of the existing disc degeneration, it is possible to differentiate between the nucleus pulposus and annulus fibrosus. 1. annulus fibrosis 2. Circumferential annular tears 3- Posterior longitudinal ligament 4. The desiccated nucleus pulposus Table 1. Factors implicated in disc aging and disc degeneration Factor Comment Nutritional compromise will deprive the disc cells of the capability to form proteoglycan. Without proteoglycans aggrecan & aggrecate, the water trapping function of the nucleus is lost, the disc losses its water content (dehydrates) and losses its hydrostatic pressure (osmotic pressure)  Idiopathic loss of the discal blood supply above the vertebral end-plates  End-plate calcification  Vascular risk factors resulting in arteriolosclerosis of tiny capillary beds that are in the subchondral bone, just above the vertebral end-plates (subchondral vascular network) Non-Enzymatic Glycation Specifically, this reaction occurs between the protein molecules within the collagen of the annulus, and free floating glucose (reduced sugar) in an avascular medium. This reaction is called 'posttranslational protein modification or Glycation. The proteins are transformed into what is called an 'Advanced Glycation End- Product' or unstable AGE. Free radical oxidation The unstable AGEs molecules is oxidize by free radical into a much more stable structure called a CML (N- Carboxymethyl - lysine). CML formation has been found to be an excellent indication of discal aging www.yassermetwally.com Professor Yasser Metwally www.yassermetwally.com
    • Figure 16. Dessication of the nucleus pulposus associated with multiple annular tears (eg, radial, circumferential). Notice that the disc is bulging without actual herniation. Because of the existing disc degeneration, it is possible to differentiate between the nucleus pulposus and annulus fibrosus. Notice the existence of articular facet pathology and tegmental flavum hypertrophy. 1. annulus fibrosis 2. Circumferential annular tears with infiltration by nuclear material 3,4 . The desiccated nucleus pulposus DISC / VERTEBRAL COLUMN PATHOLOGICAL CHANGES IN DEGENERATIVE DISC DISEASES Degenerative disc disease commonly induces pathological changes in both the intervertebral discs and the vertebral column, collectively these are called spondylosis. Table 2 Table 2. Disc/ vertebral column pathological changes in degenerative disc disease Pathology Comment Disc pathology Annular bulging, annular tears, nucleus pulposus herniation, vacuum disc, canal stenosis Pars interarticularis defect Stress fractures of one or both sides of the neural arch through the relatively weak pars. Facet pathology Facet Joint disease can be defined as osteophytosis and hypertrophy of the articular process.. etc MRI bone marrow signal changes MRI bone marrow signal changes in the vertebral endplates of the degenerated discs www.yassermetwally.com Professor Yasser Metwally www.yassermetwally.com
    • Figure 17. A, Normal spine, B, spondylosis  Role of end plate degeneration in intradiscal changes among patients with low back pain The end plate is the main route of diffusion. The nutrition provided by arterial flow is delivered through the end plate (Roberts et al. 1989, Moore et al. 1992). A comparison between end plate degeneration in MRI and intradiscal changes revealed in discography showed end plate degeneration to be associated more clearly with long-term disc damage, i.e. degeneration, than acute disc damage, i.e. annular rupture. The primary nutritional pathway into the avascular disc is assumed to be from the subchondral vessels via the end plate (Roberts et al. 1989, Moore et al. 1992). If this route were disturbed because of a calcified endplate or occlusion of the subchondral vessels, internal disc disruption could follow (Roberts et al. 1989). End plate degeneration has been found to occur parallel to other disc degeneration events (Horner & Urban 2001). Histologic studies have revealed coincidence of microfractures in the end plate and intradiscal tears and clefts (Moon et al. 2000, Boos et al. 2002). It is therefore assumed that the degenerative process affecting the end plate, the NP and the AF is a temporal sequence of nutritional deficiency (Boos et al. 2002). No differences were found between the end plate degeneration categories and pain provocation, and the results were hence opposite to the previous findings (Weishaupt et al. 2001), which showed end plate changes to be associated with low back pain. It is yet possible that the irritation of a ruptured disc by contrast medium is such a dominant factor in producing pain that minor variables, such as possible end plate irritation, will be masked, which might explain why no evident correlation between pain provocation and end plate changes was found. On the other hand, we only evaluated intradiscal pain, and the possible end plate-originated symptoms may not be discogenic. Yet, the results showed that a significant number of positive pain provocations were associated with no end plate degeneration, which also indicates the negative role of end-plate degeneration in producing low back pain. Findings of concordant pain during discography in discs with annular ruptures support the results of previous studies showing an association between intradiscal ruptures and low back pain (Vanharanta et al. 1988, Moneta et al. 1994). www.yassermetwally.com Professor Yasser Metwally www.yassermetwally.com
    • THE VASCULAR BASIS FOR DISC DEGENERATION  Arterial findings, diffusion and disc degeneration among people without low back pain Atherosclerotic changes in the lumbar arteries have been shown to be associated with lumbar disc degeneration (Kauppila et al. 1997). There is moderate variation in the findings on lumbar artery status between the disc levels. It has been demonstrated that the correlation of atherosclerotic changes with disc degeneration is stronger at the upper compared to the lower levels of the lumbar spine (Kauppila 1994) The well-being of a disc is greatly dependent on its cells (Maroudas 1988, Boos et al. 2002). The cell density of a disc is controlled by nutritional factors (Stairmand et al. 1991). During the degenerative process, considerable alterations occur in the structure and biochemistry of the intervertebral disc.  Arterial findings, disc degeneration and low back pain The major findings in the literature concerning the role of blood flow and disc degeneration can be summarised as follows. In cadaveric studies, atherosclerotic manifestations in the abdominal aorta and the lumbar arteries correlated with low back pain (Kauppila et al. 1997) and disc degeneration (Kauppila et al. 1994). In a cross-sectional cohort study, calcification of the abdominal aorta was found to correlate with disc degeneration (Kauppila et al. 1997). In some follow-up studies, vascular disease and LBP have been found to correlate (Penttinen 1994, Kauppila et al. 1997), and one post-mortem study also showed this association (Kauppila & Tallroth 1993). In epidemiological studies, low back pain and arterial disease have been found to have some common risk factors (Frymoyer & Gordon 1989, Battie et al. 1991). The nutrient supply to the nucleus cells can be disturbed at several points. Factors that affect the blood supply to the vertebral body such as vascular risk factors, the metabolic syndrome (type 2 diabetes, inulin resistance, hypertension, increased blood viscosity and atherosclerosis ...etc) can all result in disturbances of the nutrient supply to the nucleus cells and subsequent disc degeneration. Histologic and experimental studies have revealed the association between nutritional factors and disc degeneration (Horner & Urban 2001, Boos et al. 2002). It has been shown anatomically that vascular buds penetrate the cartilaginous end plates on the vertebral side, but rarely communicate with the disc substance itself (Moore et al. 1992), and that the nutrition of discs occurs mainly via diffusion from the blood vessels into the surrounding structures (Holm et al. 1981, Horner H.A. & Urban J. 2001). Thus, changes in the end plate and the vessels may cause a reduction in this pathway. www.yassermetwally.com Professor Yasser Metwally www.yassermetwally.com
    • It has been found in an experimental study that the reduction in nutrition may cause intradiscal tears and reduce the regenerative ability of cells in discs. The mechanical stress is also more likely to cause tears in conditions of reduced nutrition(Boos et al. 2002). These remaining tears could be a source of intradiscal pain and thus explain the difference in the degree of disc degeneration and lumbar artery occlusion between people with and without low back pain. Vascular changes causing insufficient blood supply in the abdominal aorta and the lumbar arteries are more common in the LBP population. Atheromatous lesions in the abdominal aorta most commonly occur around the aortic bifurcation, where the orifices of the lumbar arteries are also located (Rogoff S.M. & Lipchik E.O. 1970, Ross R 1988). Patients with chronic low back pain were more likely to have atheromatous plaques in the abdominal aorta than patients without back pain, as analysed by CT, and this association was most distinct in the youngest patients. Also, when sciatica patients were compared to an asymptomatic population, intervertebral disc degeneration and narrowing of the lumbar arteries were significantly more pronounced in the sciatic population at almost every disc level. In general, it can be concluded that the present study showed multiple evidence of an association between vascular changes and low back pain and disc degeneration. CONCLUSION 1. The metabolic syndrome (truncal obesity, type 2 diabetes, inulin resistance, hypertension, increased blood viscosity and atherosclerosis ...etc) is a risk factor for disc degeneration and back pain. Vascular risk factors can result in disturbances of the nutrient supply to the nucleus cells and subsequent disc degeneration. Disc degeneration is a vascular process rather than a mechanical one. 2. Cardiovascular/cerebrovascular risk factors are significantly and independently associated with symptomatic lumbar disc herniation. These findings provide further confirmation that atherosclerosis may be involved in spinal disc degeneration. Modification of risk factors, particularly smoking, may also prove to be beneficial. 3. Stenosis of lumbar arteries is significantly associated with decreased diffusion of lumbar discs and may thus play an important role as a mechanism of disc degeneration. 4. End plate degeneration is associated with disc degeneration, but not with disc rupture. Nor is end plate degeneration associated with discogenic pain caused by CT discography. 5. Atheromatous lesions in the abdominal aorta are more common and more extensive in patients with chronic low back pain than in asymptomatic people. There was no association between atheromatous lesions in the abdominal aorta and disc degeneration among chronic low back pain patients. 6. Stenosis of lumbar arteries is associated with disc degeneration among sciatica patients, and the grade of occlusion of lumbar arteries and the severity of disc degeneration are significantly higher among sciatica patients compared to asymptomatic subjects. 7. Stenosis of lumbar arteries was associated with back pain symptoms and physical activity among sciatica patients in three-year follow-up. www.yassermetwally.com Professor Yasser Metwally www.yassermetwally.com
    • References 1. Adams MA & Hutton WC (1982) Prolapsed intervertebral disc. A hyperflexion injury. 1981 Volvo Award in Basic Science. Spine: 184–191. 2. Adams MA & Hutton WC (1983) The effect of posture on the fluid content of lumbar intervertebral discs. Spine 8: 665–671. 3. Aguila LA, Piraino DW, Modic MT, Dudley AW, Duchesneau PM & Weinstein MA (1985) The intranuclear cleft of the intervertebral disk: magnetic resonance imaging. Radiology 155: 155–158. 4. Ahn SH, Ahn MW & Buye WM (2000) Effect of the transligamentous extension of lumbar disc herniations of their regression and the clinical outcome of sciatica. Spine 25: 475–480. 5. Aigner T, Gresk-otter KR, Fairbank JC, von d & Urban JP (1998) Variation with age in the pattern of type X collagen expression in normal and scoliotic human intervertebral discs. Calcified Tissue International 63: 263–268. 6. Akansel G, Haughton VM, Papke RA & Censky S (1997) Diffusion into human intervertebral disks studied with MR and gadoteridol. Ajnr: American Journal of Neuroradiology 18: 443–445. 7. Andersson GB, Svensson H & Oden A (1983) The intensity of work recovery in low back pain. Spine 8: 880–884. 8. Andersson GB (1998) Epidemiology of low back pain. Acta Orthopaedica Scandinavica Supplementum 281: 28–31. 9. Annunen S, Paassilta P, Lohiniva J, Perala M, Pihlajamaa T, Karppinen J, Tervonen O, Kroger H, Lahde S, Vanharanta H, Ryhanen L, Goring HH, Ott J, Prockop DJ & Ala-Kokko L (1999) An allele of COL9A2 associated with intervertebral disc disease. Science 285: 409–412. 10. Antoniou J, Goudsouzian NM, Heathfield TF, Winterbottom N, Steffen T, Poole AR, Aebi M & Alini M (1996a) The human lumbar endplate. Evidence of changes in biosynthesis and denaturation of the extracellular matrix with growth, maturation, aging, and degeneration. Spine 21: 1153–1161. 11. Antoniou J, Steffen T, Nelson F, Winterbottom N, Hollander AP, Poole RA, Aebi M & Alini M (1996b) The human lumbar intervertebral disc: evidence for changes in the biosynthesis and denaturation of the extracellular matrix with growth, maturation, ageing, and degeneration. Journal of Clinical Investigation 98: 996– 1003. 12. Antoniou J, Arlet V, Goswami T, Aebi M & Alini M (2001) Elevated synthetic activity in the convex side of scoliotic intervertebral discs and endplates compared with normal tissues. Spine 26: E198–E206. 13. Aprill C & Bogduk N (1992) High-Intensity zone: a diagnostic sign of painful lumbar disc on magnetic resonance imaging. British Journal of Radiology: 361–369. 14. Atlas SJ, Deyo RA, Keller RB, Chapin AM, Patric DL, Long JM & Singer DE (1996) The Main Lumbar Spine Study, Part II. 1 year outcomes of surcigal and nonsurgical management of sciatica. Spine 21: 1777–1786. www.yassermetwally.com Professor Yasser Metwally www.yassermetwally.com
    • 15. Axel L (1984) Surface coil magnetic resonance imaging. Journal of Computer Assisted Tomography 8: 381–384. 16. Balague F, Nordin M, Sheikhzadeh A, Echegoyen AC, Brisby H, Hoogewoud HM, Fredman P & Skovron ML (1999) Recovery of severe sciatica. Spine 24: 2516–2524. 17. Battie MC, Videman T, Gill K, Moneta GB, Nyman R, Kaprio J & Koskenvuo M (1991) 1991 Volvo Award in Clinical Sciences. Smoking and lumbar intervertebral disc degeneration: an MRI study of identical twins. Spine 16: 1015–1021. 18. Battie MC, Haynor DR, Fisher LD, Gill K, Gibbons LE & Videman T (1995a) Similarities in degenerative findings on magnetic resonance images of the lumbar spines of identical twins. J Bone Joint Surg Am 77: 1662–1670 19. Battie MC, Videman T, Gibbons LE, Fisher LD, Manninen H & Gill K (1995b) 1995 Volvo Award in Clinical Sciences. Determinants of lumbar disc degeneration. A study relating lifetime exposures and magnetic resonance imaging findings in identical twins. Spine 20: 2601–2612. 20. Baur A, Stabler A, Bruning R, Bartl R, Krodel A, Reiser M & Deimling M (1998) Diffusion-weighted MR imaging of bone marrow: differentiation of benign versus pathologic compression fractures [see comments]. Radiology 207: 349–356. 21. Biering-Sorensen F, Hansen FR, Schroll M & Runeborg O (1985) The relation of spinal x-ray to low-back pain and physical activity among 60-year-old men and women. Spine 10: 445–451. 22. Bini W, Yeung AT, Calatayud V, Chaaban A & Seferlis T (2002) The role of provocative discography in minimally invasive selective endoscopic discectomy. Neurocirugia (Asturias, Spain) 13: 27–31. 23. Boden SD, Davis DO, Dina TS, Patronas NJ & Wiesel SW (1990) Abnormal magnetic-resonance scans of the lumbar spine in asymptomatic subjects. A prospective investigation. Journal of Bone & Joint Surgery - American Volume 72: 403–408. 24. Bogduk N, Tynan W & Wilson AS (1981) The nerve supply to the human lumbar intervertebral discs. Journal of Anatomy 132: 39–56. 25. Bogduk N (1983) The innervation of lumbar spine. Spine: 286–293. 26. Bogduk N (2002). Degenerative disk disease. 85-87Vancouver, ASNR Foundation symposium. 27. Bogduk N & Modic MT (1996) Lumbar discography. Spine 21: 402–404. 28. Boos N, Weissbach S, Rohrbach H, Weiler C, Spratt K.F. & Nerlich AG (2002) Classification of Age-Related Changes in Lumbar Intervertebral Discs. 2002 Volvo Award in Basic Science. Spine 27: 2631–2644. 29. Bouissou H, Pieraggi MT & Julian M (1989) Progression, topographical aspects and regression of atherosclerosis. In Camilleri JP et al (eds) Diseases of the arterial wall. Springer-Verlag, Berlin, p 241–253. 30. Braithwaite I, White J, Saifuddin A, Renton P & Taylor BA (1998) Vertebral end- plate (Modic) changes on lumbar spine MRI: correlation with pain reproduction at lumbar discography. European Spine Journal 7: 363–368. 31. Brinckmann P & Grootenboer H (1991) Change of disc height, radial disc bulge, and intradiscal pressure from discectomy. An in vitro investigation on human lumbar discs. Spine 16: 641–646. www.yassermetwally.com Professor Yasser Metwally www.yassermetwally.com
    • 32. Brown MD (1971) The pathophysiology of disc disease. Symposium on disease of the intervertebral disc. Orthopedic Clinics of North America: 359–370. 33. Buckwalter JA (1995) Aging and degeneration of the human intervertebral disc. [Review] [20 refs]. Spine 20: 1307–1314. 34. Buckwalter JA (1999) Musculoskeletal soft tissues. In Barantz ME, Watson AD & Imbriglia JE (eds) Orthopedic surgery: The essentials. Thieme, New York, p 49–64. 35. Carey TS, Garrett J, Jackman A, McLaughlin C, Fryer J & Smucker DR (1995) The outcomes and costs of care for acute low back pain among patients seen by primary care practitioners, chiropractors, and orthopedic surgeons. The North Carolina Back Pain Project. [see comments.]. New England Journal of Medicine 333: 913–917. 36. Carey TS, Garrett JM, Jackman A & Hadler N (1999) Recurrence and care seeking after acute back pain: results of a long-term follow-up study. North Carolina Back Pain Project. Medical Care 37: 157–164. 37. Carey TS, Garrett JM & Jackman AM (2000) Beyond the good prognosis. Examination of an inception cohort of patients with chronic low back pain. Spine 25: 115–120. 38. Carragee EJ, Chen Y, Tanner CM, Hayward C, Rossi M & Hagle C (2000a) Can discography cause long-term back symptoms in previously asymptomatic subjects? Spine 25: 1803–1808. 39. Carragee EJ, Paragioudakis SJ & Khurana S (2000b) 2000 Volvo Award winner in clinical studies: Lumbar high-intensity zone and discography in subjects without low back problems. Spine 25: 2987–2992. 40. Carragee EJ, Tanner CM, Khurana S, Hayward C, Welsh J, Date E, Truong T, Rossi M & Hagle C (2000c) The rates of false-positive lumbar discography in select patients without low back symptoms. [see comments]. Spine 25: 1373–80 discussion. 41. Cassar-Pullicino VN (1998) MRI of the ageing and herniating intervertebral disc. Eur J Radiol 27: 214–228. 42. Chien D, Kwong KK, Gress DR, Buonanno FS, Buxton RB & Rosen BR (1992) MR diffusion imaging of cerebral infarction in humans. AJNR Am J Neuroradiol 13: 1097–1102. 43. Clark CA, Werring DJ & Miller DH (2000) Diffusion imaging of the spinal cord in vivo: estimation of the principal diffusivities and application to multiple sclerosis. Magnetic Resonance in Medicine 43: 133–138. 44. Cluroe AD, Fitzjohn TP & Stehbens WE (1992) Combined pathological and radiological study of the effect of atherosclerosis on the ostia of segmental branches of the abdominal aorta. Pathology 24: 410–417. 45. Constable RT, Smith RC & Gore JC (1992) Signal-to-noise and contrast in fast spin echo (FSE) and inversion recovery FSE imaging. Journal of Computer Assisted Tomography 16: 41–47. 46. Coppes MH, Marani E, Thomeer RT & Groen GJ (1997) Innervation of painful lumbar discs. Spine: 2342–2350. 47. Coventry MB, Ghormley RK & Kernohan JW (1945a) The Intervertebral disc: its microscopic anatomy and pathology. Part I. Journal of Bone & Joint Surgery: 105– 112. www.yassermetwally.com Professor Yasser Metwally www.yassermetwally.com
    • 48. Coventry MB, Ghormley RK & Kernohan JW (1945b) The intervertebral disc: its microscopic anatomy and pathology.Part II. Changes in the intervertebral disc concomitant with age. Journal of Bone & Joint Surgery 27: 233–247. 49. Coventry MB, Ghormley RK & Kernohan JW (1945c) The intervertebral disc: its microscopic anatomy and pathology. Part III. Pathological changes in the intervertebral disc. Journal of Bone & Joint Surgery 27: 460–474. 50. Crock HV & Yoshizawa H (1976) The blood supply of the lumbar vertebral column. Clinical Orthopaedics & Related Research: 6–21. 51. Deyo RA & Tsui-Wu YJ (1987) Descriptive epidemiology of low-back pain and its related medical care in the United States. Spine 12: 264–268. 52. Deyo RA & Bass JE (1989) Lifestyle and low back pain. The influence of smoking and obesity. Spine: 501–506. 53. Doran M, Hajnal JV, Van Bruggen N, King MD, Young IR & Bydder GM (1990) Normal and abnormal white matter tracts shown by MR imaging using directional diffusion weighted sequences. Journal of Computer Assisted Tomography 14: 865– 873. 54. Dullerud R & Johansen JG (1995) CT-discography in patients with sciatica. Comparison with plain CT and MR imaging. Acta Radiologica 36: 497–504. 55. Dwyer AP (1996) Clinically relevant anatomy. The lumbar spine, vol. 1. Saunders, Philadelphia, p 57–73. 56. Edelman RR, Wielopolski P & Schmitt F (1994) Echo-planar MR imaging. Radiology 192: 600–612. 57. Eriksen W, Natvig B & Bruusgaard D (1999) Smoking, heavy physical work and low back pain: a four-year prospective study. Occup Med (Lond) 49: 155–160. 58. Erkintalo MO, Salminen JJ, Alanen AM, Paajanen HE & Kormano MJ (1995) Development of degenerative changes in the lumbar intervertebral disk: results of a prospective MR imaging study in adolescents with and without low-back pain. Radiology 1995 Aug;196: 529–533. 59. Eyre DR (1979) Biochemistry of the intervertebral disc. [Review] [139 refs]. International Review of Connective Tissue Research 8: 227–291. 60. Eyre DR & Muir H (1976) Types I and II collagens in intervertebral disc. Interchanging radial distributions in annulus fibrosus. Biochemical Journal 157: 267–270. 61. Eyre DR, Benya P, Buckwalter,JA, Caterson B, Heinegard,D, Oegema,TR, Pearce R, Pope,MH, Urban J, J. (1989). The intervertebral disc: Basic science perspectives. 147-207 Illinois, American Academicy of Orthopedic Surgeons. New Perspectives of Low Back Pain. Frymoyer, J. W. and Gordon, S. L. 62. Fairbank JC, Park WM, McCall IW & O"Brien JP (1981) Apophyseal injection of local anesthetic as a diagnostic aid in primary low-back pain syndromes. Spine 6: 598–605. 63. Fortin J & Aprill CN (1994) Sacroilica joint: Pain referral maps upon applying a new injection/arthrography technique. Part II Clinical evaluation. Spine: 1483– 1489. 64. Fraser R, Osti OL & Vernon-Roberts B (1993) Intervertebral disc degeneration. European Spine Journal: 205–213. www.yassermetwally.com Professor Yasser Metwally www.yassermetwally.com
    • 65. Frymoyer JW (1988) Back pain and sciatica. [Review] [131 refs]. New England Journal of Medicine 318: 291–300. 66. Frymoyer JW & Gordon SL (1989) Research perspectives in low-back pain. Report of a 1988 workshop. Spine 14: 1384–1390 67. Frymoyer JW, Pope MH, Clements JH, Wilder DG, MacPherson B & Ashikaga T (1983) Risk factors in low-back pain. An epidemiological survey. Journal of Bone & Joint Surgery - American Volume 65: 213–218. 68. Georgy BA & Hesselink JR (1994) MR imaging of the spine: recent advances in pulse sequences and special techniques. [Review] [43 refs]. AJR American Journal of Roentgenology 162: 923–934. 69. Gibson MJ, Buckley J, Mawhinney R, Mulholland RC & Worthington BS (1986) Magnetic resonance imaging and discography in the diagnosis of disc degeneration. A comparative study of 50 discs. Journal of Bone & Joint Surgery - British Volume 68: 369–373. 70. Goldberg MS, Scott SC & Mayo NE (2000) A review of the association between cigarette smoking and the development of nonspecific back pain and related outcomes. Spine 25: 995–1014. 71. Gray L & MacFall J. (1998) Overview of diffusion imaging. Magnetic Resonance Imaging Clinics of North America: 125–138. 72. Grimshaw MJ & Mason RM (2000) Bovine articular chondrocyte function in vitro depends upon oxygen tension. Osteoarthritis & Cartilage 8: 386–392. 73. Gronblad M, Weinstein JN & Santavirta S (1991) Immunohistochemical observations on spinal tissue innervation. A review of hypothetical mechanisms of back pain. [Review] [56 refs]. Acta Orthopaedica Scandinavica 62: 614–622. 74. Gruber HE, Ma D, Hanley ENJ, Ingram J & Yamaguchi DT (2001) Morphologic and molecular evidence for gap junctions and connexin 43 and 45 expression in annulus fibrosus cells from the human intervertebral disc. Journal of Orthopaedic Research 19: 985–989. 75. Gundry CR & Fritts HM (1997) Magnetic resonance imaging of the musculoskeletal system. Part 8. The spine, section 1. Clinical Orthopaedics & Related Research: 275–287. 76. Gundry CR & Fritts HM (1998) Magnetic resonance imaging of the musculoskeletal system: the spine. Clinical Orthopaedics & Related Research: 262–278. 77. Guyer RD & Ohnmeiss DD (1995) Lumbar discography. Position statement from the North American Spine Society Diagnostic and Therapeutic Committee [see comments]. [Review] [89 refs]. Spine 20: 2048–2059. 78. Hall AC (1999) Differential effects of hydrostatic pressure on cation transport pathways of isolated articular chondrocytes. Journal of Cellular Physiology 178: 197–204. 79. Heliövaara M (1987) Body height, obesity, and risk of herniated lumbar intervertebral disc. Spine 12: 469–472. 80. Heliövaara M. (1988) Epidemiology of sciatica and herniated lumbar intervertebral disc. Academic dissertation. Publication of the Social Insurance Institution. Helsinki: 81. Heliövaara M (1989) Risk factors to low back pain and sciatica. Annals of Medicine 21: 257–264. www.yassermetwally.com Professor Yasser Metwally www.yassermetwally.com
    • 82. Herzog RJ (1996) The radiologic assessment for a lumbar disc herniation. Spine 21: 19S–38S. 83. Hirsch C & Schajowicz F (1953) Studies on structural changes in the lumbar annulus fibrosus. Acta Orthopaedica Scandinavica 22: 184–189. 84. Holm S (1993) Pathophysiology of disc degeneration. [Review] [9 refs]. Acta Orthopaedica Scandinavica Supplementum 251: 13–15. 85. Holm S (1996) Nutritional and pathophysiologic aspects of the lumbar intervertebral disc. The lumbar spine. Saunders, Philadelphia, p 285–310. 86. Holm S & Selstam G (1982) Oxygen tension alterations in the intervertebral disc as a response to changes in the arterial blood. Upsala Journal of Medical Sciences 87: 163–174. 87. Holm S & Nachemson A (1988) Nutrition of the intervertebral disc: acute effects of cigarette smoking. An experimental animal study. Upsala Journal of Medical Sciences 93: 91–99. 88. Holm S, Maroudas A, Urban JP, Selstam G & Nachemson A (1981) Nutrition of the intervertebral disc: solute transport and metabolism. Connective Tissue Research 8: 101–119. 89. Horner HA & Urban JP (2001) 2001 Volvo Award Winner in Basic Science Studies: Effect of nutrient supply on the viability of cells from the nucleus pulposus of the intervertebral disc. Spine 26: 2543–2549. 90. Horton WC & Daftari TK (1992) Which disc as visualized by magnetic resonance imaging is actually a source of pain? A correlation between magnetic resonance imaging and discography. Spine 17: Suppl-71. 91. Hrubec Z & Nashold BS, Jr. (1975) Epidemiology of lumbar disc lesions in the military in World War II. Am J Epidemiol 102: 367–376. 92. Hsu EW & Setton LA (1999) Diffusion tensor microscopy of the intervertebral disc anulus fibrosus. Magnetic Resonance in Medicine 41: 992–999. 93. Ibrahim MA, Haughton VM & Hyde JS (1994a) Enhancement of intervertebral disks with gadolinium complexes: comparison of an ionic and a nonionic medium in an animal model. Ajnr: American Journal of Neuroradiology 15: 1907–1910. 94. Ibrahim MA, Jesmanowicz A, Hyde JS, Estkowski L & Haughton VM (1994b) Contrast enhancement of normal intervertebral disks: time and dose dependence. AJNR Am J Neuroradiol 15: 419–423. 95. Ibrahim MA, Haughton VM & Hyde JS (1995) Effect of disk maturation on diffusion of low-molecular-weight gadolinium complexes: an experimental study in rabbits. Ajnr: American Journal of Neuroradiology 16: 1307–1311. 96. Indahl Aege (1999) Low back pain – a functional disturbance. Physiology and Treatment. Thesis, University of Oslo, Centre of Orthopaedics, National Hospital. 97. Ishihara H & Urban JP (1999) Effects of low oxygen concentrations and metabolic inhibitors on proteoglycan and protein synthesis rates in the intervertebral disc. Journal of Orthopaedic Research 17: 829–835. 98. Ito T, Yamada M, Ikuta F, Fukuda T, Hoshi SI, Kawaji Y, Uchiyama S, Homma T & Takahashi HE (1996) Histologic evidence of absorbtion of sequestration-type herniated disc. Spine: 230–234. 99. Jarvik JG & Deyo RA (2000a) Imaging of lumbar intervertebral disk degeneration and aging, excluding disk herniations. Radiol Clin North Am 38: 1255–66, vi. www.yassermetwally.com Professor Yasser Metwally www.yassermetwally.com
    • 100. Jarvik JG & Deyo RA (2000b) Imaging of lumbar intervertebral disk degeneration and aging, excluding disk herniations. [Review] [47 refs]. Radiologic Clinics of North America 38: 1255–1266. 101. Jensen MC, Brant-Zawadzki MN, Obuchowski N, Modic MT, Malkasian D & Ross JS (1994a) Magnetic resonance imaging of the lumbar spine in people without back pain. N Engl J Med 331: 69–73. 102. Jensen MC, Kelly AP & Brant-Zawadzki MN (1994b) MRI of degenerative disease of the lumbar spine. [Review] [60 refs]. Magnetic Resonance Quarterly 10: 173–190. 103. Jinkins JR & Runge VM (1995) The use of MR contrast agents in the evaluation of disease of the spine. [Review] [20 refs]. Topics in Magnetic Resonance Imaging 7: 168–180. 104. Jinkins JR & Van G (2001) The postsurgical lumbosacral spine. Magnetic resonance imaging evaluation following intervertebral disk surgery, surgical decompression, intervertebral bony fusion, and spinal instrumentation. [Review] [20 refs]. Radiologic Clinics of North America 39: 1–29. 105. Kaplan DM, Knapp M, Romm FJ & Velez R (1986) Low back pain and x- ray films of the lumbar spine: a prospective study in primary care. South Med J 79: 811–814. 106. Karasek M & Bogduk N (2000) Twelve-month follow-up of a controlled trial of intradiscal thermal anuloplasty for back pain due to internal disc disruption. Spine 25: 2601–2607. 107. Karppinen J, Malmivaara A, Tervonen O, Paakko E, Kurunlahti M, Syrjala P, Vasari P & Vanharanta H (2001) Severity of symptoms and signs in relation to magnetic resonance imaging findings among sciatic patients. Spine 26: E149–E154. 108. Katzen BT (1995) Current status of digital angiography in vascular imaging. Radiol Clin North Am 33: 1–14. 109. Kauppila LI (1994) Blood supply of the lower thoracic and lumbosacral regions. Postmortem aortography in 38 young adults. Acta Radiologica 35: 541–544. 110. Kauppila LI (1995) Ingrowth of blood vessels in disc degeneration. Angiographic and histological studies of cadaveric spines. Journal of Bone & Joint Surgery - American Volume 77: 26–31. 111. Kauppila LI (1997) Prevalence of stenotic changes in arteries supplying the lumbar spine. A postmortem angiographic study on 140 subjects. Annals of the Rheumatic Diseases 56: 591–595. 112. Kauppila LI & Tallroth K (1993) Postmortem angiographic findings for arteries supplying the lumbar spine: their relationship to low-back symptoms. Journal of Spinal Disorders 6: 124–129. 113. Kauppila LI, Penttila A, Karhunen PJ, Lalu K & Hannikainen P (1994) Lumbar disc degeneration and atherosclerosis of the abdominal aorta. Spine 19: 923–929. 114. Kauppila LI, McAlindon T, Evans S, Wilson PW, Kiel D & Felson DT (1997) Disc degeneration/back pain and calcification of the abdominal aorta. A 25-year follow-up study in Framingham. Spine 22: 1642–1647. 115. Kawakami M, Tamaki T, Hayashi N, Hashizume K, Matsumoto T, Minamide A & Kihira T (2000) Mechanical compression of the nerve root alters www.yassermetwally.com Professor Yasser Metwally www.yassermetwally.com
    • pain related behaviors induced by the nucleus pulposus in the rat. J Orthop Res 18: 257–264. 116. Kayama S, Konno S, Olmarker K, Yabuki S & Kikuchi S (1996) Incision of the annulus fibrosus induces nerve root morphologic, vascular, and functional changes. An experimental study. Spine: 2539–2543. 117. Kelsey JL, Githens PB, White AA, III, Holford TR, Walter SD, O"Connor T, Ostfeld AM, Weil U, Southwick WO & Calogero JA (1984) An epidemiologic study of lifting and twisting on the job and risk for acute prolapsed lumbar intervertebral disc. J Orthop Res 2: 61–66. 118. Kerttula LI, Jauhiainen JP, Tervonen O, Suramo IJ, Koivula A & Oikarinen JT (2000) Apparent diffusion coefficient in thoracolumbar intervertebral discs of healthy young volunteers. Journal of Magnetic Resonance Imaging 12: 255–260. 119. Korosec FR & Mistretta CA (1998) MR angiography: basic principles and theory. Magn Reson Imaging Clin N Am 6: 223–256. 120. Kääpä E, Holm S, Inkinen R, Lammi MJ, Tammi M & Vanharanta H (1994) Proteoglycan chemistry in experimentally injured porcine intervertebral disk. J Spinal Disord 7: 296–306. 121. Lam KS, Carlin D & Mulholland RC (2000) Lumbar disc high-intensity zone: the value and significance of provocative discography in the determination of the discogenic pain source. European Spine Journal 9: 36–41. 122. Larsson HB, Thomsen C, Frederiksen J, Stubgaard M & Henriksen O (1992) In vivo magnetic resonance diffusion measurement in the brain of patients with multiple sclerosis. Magnetic Resonance Imaging 10: 7–12. 123. Last RJ (1978). Anatomy, regional and applied. 6, 306-308 Edinburgh, Churchill Livingstone. 124. Le Bihan D (1991) Molecular diffusion nuclear magnetic resonance imaging. Magn Reson Q 7: 1–30. 125. Le Bihan DJ (1998) Differentiation of benign versus pathologic compression fractures with diffusion-weighted MR imaging: a closer step toward the "holy grail" of tissue characterization? [editorial; comment]. Radiology 207: 305–307. 126. Le Bihan D, Breton E, Lallemand D, Grenier P, Cabanis E & Laval-Jeantet M (1986) MR imaging of intravoxel incoherent motions: application to diffusion and perfusion in neurologic disorders. Radiology 161: 401–407. 127. Le Bihan D, Breton E, Lallemand D, Aubin ML, Vignaud J & Laval-Jeantet M (1988) Separation of diffusion and perfusion in intravoxel incoherent motion MR imaging. Radiology 168: 497–505. 128. Le Bihan D, Turner R, Douek P & Patronas N (1992) Diffusion MR imaging: clinical applications. AJR Am J Roentgenol 159: 591–599. 129. Leboeuf-Yde C (1999) Smoking and low back pain. A systematic literature review of 41 journal articles reporting 47 epidemiologic studies. [Review] [53 refs]. Spine 24: 1463–1470. 130. Leboeuf-Yde C (2000) Body weight and low back pain. A systematic literature review of 56 journal articles reporting on 65 epidemiologic studies. Spine 25: 226–237. www.yassermetwally.com Professor Yasser Metwally www.yassermetwally.com
    • 131. Lee CK, Rauschning W & Glenn W (1988) Lateral lumbar spinal canal stenosis: classification, pathologic anatomy and surgical decompression. Spine: 313– 320. 132. Lee SH, Coleman PE & Hahn FJ (1988) Magnetic resonance imaging of degenerative disk disease of the spine. Radiol Clin North Am 26: 949–964. 133. Lehmann KJ, Weisser G, Neff KW, Mai SK, Denk S & Georgi M (1999) First results of computerised tomographic angiography using electron beam tomography. Eur Radiol 9: 625–629. 134. Lorentz M & Patwarhan AG (1996) The three-joint complex. The lumbar spine, vol. 1. Saunders, Philadelphia, p 52–57. 135. Luoma K, Riihimaki H, Luukkonen R, Raininko R, Viikari-Juntura E & Lamminen A (2000) Low back pain in relation to lumbar disc degeneration. Spine 25: 487–492. 136. Luoma K, Vehmas T, Riihimaki H & Raininko R (2001) Disc height and signal intensity of the nucleus pulposus on magnetic resonance imaging as indicators of lumbar disc degeneration. Spine 26: 680–686. 137. Magora A (1973) Investigation of the relation between low back pain and occupation. V. Psychological aspects. Scand J Rehabil Med 5: 191–196. 138. Maroudas A, Stockwell RA, Nachemson A & Urban J (1975) Factors involved in the nutrition of the human lumbar intervertebral disc: cellularity and diffusion of glucose in vitro. Journal of Anatomy 120: 113–130. 139. Maroudas A, Weinberg PD, Parker KH & Winlove CP (1988) The distributions and diffusivities of small ions in chondroitin sulphate, hyaluronate and some proteoglycan solutions. Biophysical Chemistry 32: 257–270. 140. Marras WS, Davis KG, Heaney CA, Maronitis AB & Allread WG (2000) The influence of psychosocial stress, gender, and personality on mechanical loading of the lumbar spine. Spine 25: 3045–3054. 141. Masaryk TJ, Ross JS, Modic MT, Boumphrey F, Bohlman H & Wilber G (1988) High-resolution MR imaging of sequestered lumbar intervertebral disks. AJR Am J Roentgenol 150: 1155–1162. 142. McCarron RF, Wimpee MW, Hudkins PG & Laros GS (1987) The inflammatory effect of nucleus pulposus. A possible element in the pathogenesis of low back pain. Spine: 760–764. 143. Merriam WF, Burwell RG, Mulholland RC, Pearson JC & Webb JK (1983) A study revealing a tall pelvis in subjects with low back pain. J Bone Joint Surg Br 65: 153–156. 144. Milette PC (2000) Classification, diagnostic imaging, and imaging characterization of a lumbar herniated disk. [Review] [94 refs]. Radiologic Clinics of North America 38: 1267–1292. 145. Mirowitz SA. (1996). Pitfalls, Variants and artifacts in Body MR imaging. St Louis: Mosby-Year Book 146. Mobasheri A, Hall AC, Urban JP, France SJ & Smith AL (1997) Immunologic and autoradiographic localisation of the Na+, K(+)-ATPase in articular cartilage: upregulation in response to changes in extracellular Na+ concentration. International Journal of Biochemistry & Cell Biology 29: 649–657. www.yassermetwally.com Professor Yasser Metwally www.yassermetwally.com
    • 147. Modic MT, Pavlicek W, Weinstein MA, Boumphrey F, Ngo F, Hardy R & Duchesneau PM (1984) Magnetic resonance imaging of intervertebral disk disease. Clinical and pulse sequence considerations. Radiology 152: 103–111. 148. Modic MT, Masaryk TJ, Ross JS & Carter JR (1988a) Imaging of degenerative disk disease. [Review] [76 refs]. Radiology 168: 177–186. 149. Modic MT, Steinberg PM, Ross JS, Masaryk TJ & Carter JR (1988b) Degenerative disk disease: assessment of changes in vertebral body marrow with MR imaging. Radiology 166: 193–199. 150. Moneta GB, Videman T, Kaivanto K, Aprill C, Spivey M, Vanharanta H, Sachs BL, Guyer RD, Hochschuler SH & Raschbaum RF (1994) Reported pain during lumbar discography as a function of anular ruptures and disc degeneration. A re-analysis of 833 discograms. Spine 19: 1968–1974. 151. Moon SH, Gilbertson LG, Nishida K, Knaub M, Muzzonigro T, Robbins PD, Evans CH & Kang JD (2000) Human intervertebral disc cells are genetically modifiable by adenovirus-mediated gene transfer: implications for the clinical management of intervertebral disc disorders. Spine 25: 2573–2579. 152. Mooney V (1989) Where is the lumbar pain coming from? Ann Med 21: 373– 379. 153. Moore KL. (1985). Clincally oriented anatomy. Williams and Wilkins Ltd. 154. Moore RJ (2000) The vertebral end-plate: what do we know? [Review] [50 refs]. European Spine Journal 9: 92–96. 155. Moore RJ, Osti OL, Vernon-Roberts B & Fraser RD (1992) Changes in end plate vascularity after an outer anulus tear in the sheep. Spine 17: 874–878. 156. Morgan S & Saifuddin A (1999) MRI of the lumbar intervertebral disc. [Review] [73 refs]. Clinical Radiology 54: 703–723. 157. Muller MF, Prasad P, Siewert B, Nissenbaum MA, Raptopoulos V & Edelman RR (1994) Abdominal diffusion mapping with use of a whole-body echo- planar system. Radiology 190: 475–478. 158. Murayama S, Numaguchi Y & Robinson AE (1990) Degenerative lumbar spine disorders in gradient refocused echo axial magnetic resonance images. Clinical Imaging 14: 198–203. 159. Nachemson A (1989) Lumbar discography--where are we today? [see comments]. Spine 14: 555–557. 160. Nguyen-minh C, Riley L, III, Ho KC, Xu R, An H & Haughton VM (1997) Effect of degeneration of the intervertebral disk on the process of diffusion. Ajnr: American Journal of Neuroradiology 18: 435–442. 161. Nguyen-minh C, Haughton VM, Papke RA, An H & Censky SC (1998) Measuring diffusion of solutes into intervertebral disks with MR imaging and paramagnetic contrast medium. Ajnr: American Journal of Neuroradiology 19: 1781–1784. 162. O"Neill TW, McCloskey EV, Kanis JA, Bhalla AK, Reeve J, Reid DM, Todd C, Woolf AD & Silman AJ (1999) The distribution, determinants, and clinical correlates of vertebral osteophytosis: a population based survey. J Rheumatol 26: 842–848. www.yassermetwally.com Professor Yasser Metwally www.yassermetwally.com
    • 163. Ohnmeiss DD, Vanharanta H & Ekholm J (1999a) Relation between pain location and disc pathology: a study of pain drawings and CT/discography. Clinical Journal of Pain 15: 210–217. 164. Ohnmeiss DD, Vanharanta H & Ekholm J (1999b) Relation between pain location and disc pathology: a study of pain drawings and CT/discography. Clinical Journal of Pain 15: 210–217. 165. Ohshima H, Tsuji H, Hirano N, Ishihara H, Katoh Y & Yamada H (1989) Water diffusion pathway, swelling pressure, and biomechanical properties of the intervertebral disc during compression load. Spine 14: 1234–1244. 166. Olmarker K, Blomquist J, Stromberg J, Nannmark U, Thomsen P & Rydevik B (1995) Inflammatogenic properties of nucleus pulposus. Spine 20: 665– 669. 167. Olmarker K, Iwabuchi M, Larsson K & Rydevik B (1998) Walking analysis of rats subjected to experimental disc herniation. European Spine Journal 7: 394– 399. 168. Osti OL & Fraser RD (1992) MRI and discography of annular tears and intervertebral disc degeneration. A prospective clinical comparison. [see comments]. [erratum appears in J Bone Joint Surg Br 1992 Sep;74(5):793]. Journal of Bone & Joint Surgery - British Volume 74: 431–435. 169. Osti OL & Cullum DE (1994) Occupational low back pain and intervertebral disc degeneration: epidemiology, imaging, and pathology. [Review] [36 refs]. Clinical Journal of Pain 10: 331–334. 170. Osti OL, Vernon-Roberts B, Moore R & Fraser RD (1992a) Annular tears and disc degeneration in the lumbar spine. A post-mortem study of 135 discs. Journal of Bone & Joint Surgery - British Volume 74: 678–682. 171. Osti OL, Vernon-Roberts B, Moore R & Fraser RD (1992b) Annular tears and disc degeneration in the lumbar spine. A post-mortem study of 135 discs. Journal of Bone & Joint Surgery - British Volume 74: 678–682. 172. Paajanen H, Erkintalo M, Parkkola R, Salminen J & Kormano M (1997) Age-dependent correlation of low-back pain and lumbar disc regeneration. Arch Orthop Trauma Surg 116: 106–107. 173. Palmgren T, Gronblad M, Virri J, Kaapa E & Karaharju E (1999) An immunohistochemical study of nerve structures in the anulus fibrosus of human normal lumbar intervertebral discs. Spine 24: 2075–2079. 174. Parkkola R, Rytokoski U & Kormano M (1993) Magnetic resonance imaging of the discs and trunk muscles in patients with chronic low back pain and healthy control subjects. Spine 18: 830–836. 175. Penttinen J (1994) Back pain and risk of fatal ischaemic heart disease: 13 year follow up of Finnish farmers. BMJ 309: 1267–1268. 176. Pfirrmann CW, Metzdorf A, Zanetti M, Hodler J & Boos N (2001) Magnetic resonance classification of lumbar intervertebral disc degeneration. Spine 26: 1873– 1878. 177. Pierpaoli C, Jezzard P, Basser BJ, Barnet A & DiChiro G (1996) Diffusion tensor MR imaging of the human brain. Radiology: 637–648. www.yassermetwally.com Professor Yasser Metwally www.yassermetwally.com
    • 178. Power C, Frank J, Hertzman C, Schierhout G & Li L (2001) Predictors of low back pain onset in a prospective British study. Am J Public Health 91: 1671– 1678. 179. Pritzker KP (1977) Aging and degeneration in the lumbar intervertebral disc. Orthopedic Clinics of North America 8: 66–77. 180. Ratcliffe JF (1982) The anatomy of the fourth and fifth lumbar arteries in humans: an arteriographic study in one hundred live subjects. Journal of Anatomy 135: 753–761. 181. Razaq S, Urban JP & Wilkins RJ (2000) Regulation of intracellular pH by bovine intervertebral disc cells. Cellular Physiology & Biochemistry 10: 109–115. 182. Resnick D (1985) Degenerative diseases of the vertebral column. Radiology 156: 3–14. 183. Riihimäki H, Wickstrom G, Hanninen K & Luopajarvi T (1989a) Predictors of sciatic pain among concrete reinforcement workers and house painters--a five- year follow-up. Scandinavian Journal of Work, Environment & Health 1989 Dec;15: 415–423. 184. Riihimäki H, Wickstrom G, Hanninen K, Mattsson T, Waris P & Zitting A (1989b) Radiographically detectable lumbar degenerative changes as risk indicators of back pain. A cross-sectional epidemiologic study of concrete reinforcement workers and house painters. [see comments]. Scandinavian Journal of Work, Environment & Health 1989 Aug;15: 280–285. 185. Riihimäki H, Mattsson T, Zitting A, Wickstrom G, Hanninen K & Waris P (1990) Radiographically detectable degenerative changes of the lumbar spine among concrete reinforcement workers and house painters. Spine 15: 114–119. 186. Roberts S, Menage J & Urban JP (1989) Biochemical and structural properties of the cartilage end-plate and its relation to the intervertebral disc. Spine 14: 166–174. 187. Roberts S, Menage J & Eisenstein SM (1993) The cartilage end-plate and intervertebral disc in scoliosis: calcification and other sequelae. Journal of Orthopaedic Research 11: 747–757. 188. Roberts S, Urban JP, Evans H & Eisenstein SM (1996) Transport properties of the human cartilage endplate in relation to its composition and calcification. Spine 21: 415–420. 189. Rogoff S.M, Lipchik E.O (1970) Lumbar aortography in arteriosclerosis. Abrams H.L. 2nd ed., 737-757 New York, Churchill Livingstone. Angiography. 190. Ross R (1988). Atherosclerosis. 318-323Philadelphia, WB Saunders. Cecil Textbook of Medicine. Wyngaarden J.B. and Smith L.H. 191. Ross JS, Ruggieri P, Tkach J, Obuchowski N, Dillinger J, Masaryk TJ & Modic MT (1993) Lumbar degenerative disk disease: prospective comparison of conventional T2-weighted spin-echo imaging and T2-weighted rapid acquisition relaxation-enhanced imaging. Ajnr: American Journal of Neuroradiology 14: 1215– 1223. 192. Rubin GD, Dake MD & Semba CP (1995) Current status of three- dimensional spiral CT scanning for imaging the vasculature. Radiol Clin North Am 33: 51–70. www.yassermetwally.com Professor Yasser Metwally www.yassermetwally.com
    • 193. Ruggieri P (1999) Pulse sequences in lumbar spine imaging. Magnetic Resonance Imaging Clinics of North America 7: 425–437. 194. Saal JA & Saal JS (1990) The natural history of lumbar intervertebral disc extrusions treated nonoperatively. Spine: 683–686. 195. Sachs BL, Vanharanta H, Spivey MA, Guyer RD, Videman T, Rashbaum RF, Johnson RG, Hochschuler SH & Mooney V (1987) Dallas discogram description. A new classification of CT/discography in low-back disorders. Spine 12: 287–294. 196. Sambrook PN, MacGregor AJ & Spector TD (1999) Genetic influences on cervical and lumbar disc degeneration: a magnetic resonance imaging study in twins. Arthritis Rheum 42: 366–372. 197. Sandhu HS, Sanchez-Caso LP, Parvataneni HK, Cammisa FPJ, Girardi FP & Ghelman B (2000) Association between findings of provocative discography and vertebral endplate signal changes as seen on MRI. Journal of Spinal Disorders 13: 438–443. 198. Saunders JB & Inman VT (1940) Pathology of the intervertebral disc. Arch Surg: 389–416. 199. Schellhas KP, Pollei SR, Gundry CR & Heithoff KB (1996) Lumbar disc high-intensity zone. Correlation of magnetic resonance imaging and discography. Spine 21: 79–86. 200. Schenk JF (1996) The role of magnetic susceptibility in magnetic resonance imaging: MRI magnetic compatibly of the first and second kinds. Med Phys: 815– 845. 201. Schiebler ML, Grenier N, Fallon M, Camerino V, Zlatkin M & Kressel HY (1991) Normal and degenerated intervertebral disk: in vivo and in vitro MR imaging with histopathologic correlation. AJR Am J Roentgenol 157: 93–97. 202. Selby D, Henderson R, Blumenthal S, Dossett D (1987). Anterior lumbar fusion. White A, Rothman RH, Ray CD. 384St. Louis, CV Mosby. Lumbar Spine Surgery. 203. Sheppard S (1995) Basic concepts in magnetic resonance angiography. Radiol Clin North Am 33: 91–113. 204. Sihvonen T (1992) The segmental dorsal ramus neuropathy as a common cause of chronic and recurrent low back pain. Electromyogr clin Neurophysiol: 507–510. 205. Smyth RH & Grist TM (1998) MR angiography of the abdominal aorta. Magn Reson Imaging Clin N Am 6: 321–329. 206. Stadnik TW, Lee RR, Coen HL, Neirynck EC, Buisseret TS & Osteaux MJ (1998) Annular tears and disk herniation: prevalence and contrast enhancement on MR images in the absence of low back pain or sciatica. Radiology 206: 49–55. 207. Stairmand JW, Holm S & Urban JP (1991) Factors influencing oxygen concentration gradients in the intervertebral disc. A theoretical analysis. Spine 16: 444–449. 208. Stefanovic-Racic M, Stadler J, Georgescu HI & Evans CH (1994) Nitric oxide and energy production in articular chondrocytes. Journal of Cellular Physiology 159: 274–280. www.yassermetwally.com Professor Yasser Metwally www.yassermetwally.com
    • 209. Stockwell R (1971) The interrelationship of cell density and cartillage thickness in mammalian articular cartillage. Journal of Anatomy 109: 411–422. 210. Svensson H, Vedin A, Wilhelmsson C & Andersson GB (1983) Low back pain in relation to other disease and cardiovascular risk factors. Spine: 277–285. 211. Swischuk LE, John SD & Allbery S (1998) Disk degenerative disease in childhood: Scheuermann"s disease, Schmorl"s nodes, and the limbus vertebra: MRI findings in 12 patients. Pediatr Radiol 28: 334–338. 212. Szumowski J & Simon JM (1991) Proton chemical shift imaging. In Stark DD & Bradley WG Jr (eds) Magnetic resonance imaging, 2 ed. CV Mosby, St Louis, p 471–521. 213. Särkioja T (1989). Aortic atherosclerotic and related lesions in a forensic autopsy: A study of sudden coronary death in men under 50 years of age. Acta Univ Oul D. 214. Tallroth K (1998) Plain CT of the degenerative lumbar spine. [Review] [29 refs]. European Journal of Radiology 27: 206–213. 215. Taylor JR, Twomey LT (1988). The development of the human intervertebral disc. 39-82Boca Raton, Florida, CRC Press. The biology of intervertebral disc. Ghosh, P. 216. Taylor TK, Ghosh P & Bushell GR (1981) The contribution of the intervertebral disk to the scoliotic deformity. [Review] [105 refs]. Clinical Orthopaedics & Related Research: 79–90. 217. Tehranzadeh J (1998) Discography 2000. [Review] [107 refs]. Radiologic Clinics of North America 36: 463–495. 218. Tejada C, Strong JP, Montenegro MR, Restrepo C & Solberg LA (1968) Distribution of coronary and aortic atherosclerosis by geographic location, race and sex. Lab Invest 18: 509–526. 219. Tertti M, Paajanen H, Laato M, Aho H, Komu M & Kormanc M (1991) Disc degeneration in magnetic resonance imaging. A comparative biochemical, histologic, and radiologic study in cadaver spines. Spine 16: 629–634. 220. Tervonen O & Videman T (1988) Comparison of ultrasound and discography for the evaluation of lumbar disc changes. An experimental study. Neuro -Orthopedics 6: 81–86. 221. Thompson JP, Pearce RH, Schechter MT, Adams ME, Tsang IK & Bishop PB (1990) Preliminary evaluation of a scheme for grading the gross morphology of the human intervertebral disc. Spine 15: 411–415. 222. Tolly E (1984) [Transabdominal sonography of the lumbar intervertebral disks and intraspinal structures]. [German]. Rofo: Fortschritte auf dem Gebiete der Rontgenstrahlen und der Nuklearmedizin 141: 546–555. 223. Toyone T, Takahashi K, Kitahara H, Yamagata M, Murakami M & Moriya H (1994) Vertebral bone-marrow changes in degenerative lumbar disc disease. An MRI study of 74 patients with low back pain. J Bone Joint Surg Br 76: 757–764. 224. Tveten L (1976) Spinal cord vascularity. L. Extraspinal sources of spinal cord arteries in man. Acta Radiologica 17: 1–16. 225. Urban JPG (1993). The effect of physical factors on disc cell metabolism. Buckwalter,JA, Goldberg VM,Voo SLV. Musculoskeletal Sof-Tissue Aging: Impact of mobility. 391-41, IL:American Academy of Orthopaedic surgeons. www.yassermetwally.com Professor Yasser Metwally www.yassermetwally.com
    • 226. Urban JP & Maroudas A (1981) Swelling of the intervertebral disc in vitro. Connective Tissue Research 9: 1–10. 227. Urban JP & McMullin JF (1988) Swelling pressure of the lumbar intervertebral discs: influence of age, spinal level, composition, and degeneration. Spine 13: 179–187. 228. Urban JP, Holm S & Maroudas A (1978) Diffusion of small solutes into the intervertebral disc: as in vivo study. Biorheology 15: 203–221. 229. Urban JP, Holm S, Maroudas A & Nachemson A (1982) Nutrition of the intervertebral disc: effect of fluid flow on solute transport. Clinical Orthopaedics & Related Research: 296–302. 230. Urban MR, Fairbank JC, Etherington PJ, Loh FRCA, Winlove CP & Urban JP (2001) Electrochemical measurement of transport into scoliotic intervertebral discs in vivo using nitrous oxide as a tracer. Spine 26: 984–990. 231. Vanharanta H, Sachs BL, Spivey MA, Guyer RD, Hochschuler SH, Rashbaum RF, Johnson RG, Ohnmeiss D & Mooney V (1987) The relationship of pain provocation to lumbar disc deterioration as seen by CT/discography. Spine 12: 295–298. 232. Vanharanta H, Guyer RD, Ohnmeiss DD, Stith WJ, Sachs BL, Aprill C, Spivey M, Rashbaum RF, Hochschuler SH & Videman T (1988a) Disc deterioration in low-back syndromes. A prospective, multi-center CT/discography study. Spine 13: 1349–1351. 233. Vanharanta H, Sachs BL, Spivey M, Hochschuler SH, Guyer RD, Rashbaum RF, Ohnmeiss DD & Mooney V (1988b) A comparison of CT/discography, pain response and radiographic disc height. Spine 13: 321–324. 234. Varlotta GP, Brown MD, Kelsey JL & Golden AL (1991) Familial predisposition for herniation of a lumbar disc in patients who are less than twenty- one years old. J Bone Joint Surg Am 73: 124–128. 235. Vernon-Roberts B (1992) Age-related and degenerative pathology of intervertebral discs and apophyseal joints. In Jayson MI (ed) The Lumbar Spine and Back Pain. Churchill Livingstone, Edinburgh, Scotland, 17–41. 236. Vernon-Roberts B & Pirie CJ (1977) Degenerative changes in the intervertebral discs of the lumbar spine and their sequelae. Rheumatology & Rehabilitation 16: 13–21. 237. Videman T, Sarna S, Battie MC, Koskinen S, Gill K, Paananen H & Gibbons L (1995) The long-term effects of physical loading and exercise lifestyles on back- related symptoms, disability, and spinal pathology among men. Spine 20: 699–709. 238. Vihert AM (1976) Atherosclerosis of the aorta in five towns. Bulletin of the World Health Organization 53: 501–508. 239. Wallace AL, Wyatt BC, McCarthy ID & Hughes SP (1994) Humoral regulation of blood flow in the vertebral endplate. Spine 19: 1324–1328. 240. Warach S, Gaa J, Siewert B, Wielopolski P & Edelman RR (1995) Acute human stroke studied by whole brain echo planar diffusion-weighted magnetic resonance imaging. Ann Neurol 37: 231–241. 241. Wassilev W & Kuhnel W (1992) Struktur und Funktion der Zwischenwirbelscheibe. ann Anat: 154–165. www.yassermetwally.com Professor Yasser Metwally www.yassermetwally.com
    • 242. Weishaupt D, Zanetti M, Hodler J & Boos N (1998) MR imaging of the lumbar spine: prevalence of intervertebral disk extrusion and sequestration, nerve root compression, end plate abnormalities, and osteoarthritis of the facet joints in asymptomatic volunteers. Radiology 209: 661–666. 243. Weishaupt D, Zanetti M, Hodler J, Min K, Fuchs B, Pfirrmann CW & Boos N (2001) Painful Lumbar Disk Derangement: Relevance of Endplate Abnormalities at MR Imaging. Radiology 218: 420–427. 244. Wood KB, Garvey TA, Gundry C & Heithoff KB (1995) Magnetic resonance imaging of the thoracic spine. Evaluation of asymptomatic individuals. J Bone Joint Surg Am 77: 1631–1638. 245. Yamada I, Aung W, Himeno Y, Nakagawa T & Shibuya H (1999) Diffusion coefficients in abdominal organs and hepatic lesions: evaluation with intravoxel incoherent motion echo-planar MR imaging. Radiology 210: 617–623. 246. Yu SW, Haughton VM, Ho PS, Sether LA, Wagner M & Ho KC (1988a) Progressive and regressive changes in the nucleus pulposus. Part II. The adult. Radiology 169: 93–97. 247. Yu SW, Sether LA, Ho PS, Wagner M & Haughton VM (1988b) Tears of the anulus fibrosus: correlation between MR and pathologic findings in cadavers. Ajnr: American Journal of Neuroradiology 9: 367–370. 248. Yu SW, Haughton VM, Sether LA, Ho KC & Wagner M (1989) Criteria for classifying normal and degenerated lumbar intervertebral disks. Radiology 170: 523–526. 249. Yu SW, Haughton VM & Rosenbaum AE (1991) Magnetic resonance imaging and anatomy of the spine. Radiologic Clinics of North America 29: 691– 710. 250. Zucherman J, Derby R, Hsu K, Picetti G, Kaiser J, Schofferman J, Goldthwaite N & White A (1988) Normal magnetic resonance imaging with abnormal discography. Spine 13: 1355–1359. www.yassermetwally.com Professor Yasser Metwally www.yassermetwally.com