Morphological and Histological Changes in Ligamentum Flavum in Degenerative Lumbar Canal Stenosis

MORPHOLOGICAL AND HISTOLOGICAL CHANGES IN LIGAMENTUM FLAVUM IN DEGENERATIVE LUMBAR CANAL STENOSIS

Thesis submitted to the Datta Meghe Institute of Medical Sciences (Deemed University), Nagpur For the degree of PhD (Doctor of Philosophy in Orthopaedics)

Department of Orthopaedics Jawaharlal Nehru Medical College & Acharya Vinoba Bhave Rural Hospital Sawangi, Wardha Datta Meghe Institute Of Medical Sciences (Deemed University)

2012 - 2014 MORPHOLOGICAL AND HISTOLOGICAL CHANGES IN LIGAMENTUM FLAVUM IN DEGENERATIVE LUMBAR CANAL STENOSIS

A THESIS FOR

PhD (ORTHOPAEDICS)

BY DR. RATNAKAR AMBADE Professor, Department of Orthopaedics Jawaharlal Nehru Medical College, Sawangi(M),Wardha.

GUIDE DR. N. K SAXENA Professor, Department of Orthopaedics Jawaharlal Nehru Medical College, Sawangi(M), Wardha.

Department of Orthopaedics Jawaharlal Nehru Medical College & Acharya Vinoba Bhave Rural Hospital Sawangi, Wardha Datta Meghe Institute Of Medical Sciences (Deemed University)

2012 - 2014

I N D E X

Sr. No. Chapter Page No.

1. Introduction 01

2. Review of Literature 05

3. Aim and Objectives 72

4. Materials and Methods 73

5. Observations & Results 83

6. Discussion 102

7. Summary & Conclusion 112

8. Bibliography 115

Introduction

INTRODUCTION:

Back pain has been known since the start of written history, probably the first report of back pain and sciatica can be found in an ancient text, the so-called Edwin Smith

Surgical Papyrus presumably written around 1550 B.C.1

‘It's not so much the pain the man has, it is more the man who has the pain’, said

Ian Macnab in 1950.2

In the industrialised countries, back pain today is the second most common reason for seeking medical care.3 Everybody belonging to this group of ‘BACKPAIN’ wants an answer to their sufferings and in process the Governments health care budget’s share for backache goes up to billions per year and increasing year after year.

Although backache (with or without sciatica) is a benign often self -limiting condition

(Macnab).2 The cost of both time lost from work (with loss of productivity) and medical care, as well as the cost of litigation and disability claims, make back pain an in- dustry unto itself.

80% of men will have an episode of low back pain during their lifetime.3

Further facts that reveal the extent of low back pain as a problem for society are as follows:

• In the United States, at any one time, there are 1.2 million low-back-disabled

adults.4

• In the United Kingdom, 1 in 25 men changes his job each year because of a low

back pain5

It is difficult to calculate the cost of low back pain, because there are so many sources of payment to an injured worker.

1 Introduction

These include (a) wages that are paid during the waiting period before compensation from workmen's compensation insurance

(b) Group and individual health insurance plans, and

Since spinal disorders result in high costs to society, there have been an increasing number of economic evaluations.

Van Roer, Boos and van Tulder recently gave an introduction to cost analysis.

The economic burden of spinal disorders includes:

1) direct — concern medical expenditure

2) Indirect — consist of lost work output attributable to a reduced capacity for

activity, and result from lost productivity.

3) Intangible costs——are the most difficult to estimate. Intangible costs include

psychosocial burdens resulting in reduced quality of life, such as job stress,

economic stress, family stress, and suffering. The direct and indirect costs are

considerable and their management utilises a significant part of the gross na-

tional product of many countries. However, back pain has a severe impact on

the individual, families, and society.6

The most common spinal disorder in elderly patients is lumbar spinal canal stenosis, which may lead to low back and leg pain, and paresis. Canal narrowing, in part, results from hypertrophy of the ligamentum flavum.7-10

8 In 1913, Elsberg first reported the case showing sciatica caused by the ligamentum flavum hypertrophy. Afterwards, many clinical reports followed to indicate that ligamentum flavum hypertrophy was the main pathology inducing significant clinical symptoms in patients with lumbar spinal canal stenosis.8-11

2 Introduction

Since then, others have suggested that the ligamentum flavum plays an important role in the spinal disease, most prominently spinal stenosis.7-10

Furthermore, it is postulated that the ligamentum flavum hypertrophied may loose its elasticity and, thus, fold into spinal canal, which leads the compression of the dural tube.11

JB Park et. al9 clarified hypertrophy by measuring the thickness of ligamentum flavum in patients with lumbar spinal canal stenosis.

Spinal stenosis is a narrowing of the spinal canal by a combination of bone and soft tissues, which causes mechanical compression of spinal nerve roots. The compression of these nerve roots can be asymptomatic, but it can also become symptomatic, resulting in weakness, reflex alterations, gait disturbances, bowel or bladder dysfunction, motor and sensory changes, radicular pain or atypical leg pain, and neurogenic claudication.12

The ligamentum flavum attaches to the ventral side of the vertebral arch and makes up the posterior wall of the spinal canal or foramen. Ligamentum flavum is considered to be one of the important factors in the causes of radiculopathy or cauda equina symptoms in lumbar degenerative disease.13, 14, 15

It is reported that in clinical and anatomical biomechanics, the ligamentum flavum bulges inside the spinal canal or foramen at the extension position of the lumbar spine and compresses nerve tissues.16 - 21

One of the reasons may be the change in thickness of the ligament, accompanied by distance shortening between the adjacent vertebral arches.22

3 Introduction

It is also reported that foraminal stenosis occurs due to degenerative changes of the lumbar spine, such as a decrease in disc height16,23,24 and volume redistribution of the ligamentum involves nerve compression inside of the foramen.25

Thus, the morphological changes of the ligamentum flavum that are due to the change of lumbar spine alignment, as well as decrease in disc height associated with degeneration, may result in compression on nerve tissues. Ligamentum flavum undergo slight fibrotic and chondrometaplastic changes with aging. No peculiar changes occur in patients with disc herniations. In spinal stenosis, fibrotic changes, chondroid metaplasia, and calcification reduce the elasticity of the ligaments, which may thus bulge into the spinal canal in the standing position even if they are normal in thickness.26

Degenerative lumbar spinal stenosis may originate from formation of osteophytes and or ligamentous hypertrophy. As the ligamentum flavum covers most of the posterior and lateral part of the lumbar spinal canal, morphological and histological changes merit special attention in the development of lumbar spinal canal encroachment. 27

The present study was undertaken to know about morphological and histological changes that occur in ligamentum flavum with aging, in spinal stenosis and disc herniations.

4 Review of Literature

REVIEW OF LITERATURE:

HISTORY:

Spinal Stenosis

The first evidence of spinal stenosis can be found in Egyptian mummies. The first report of a spinal stenosis is attributed to the French surgeon Antoine Portal (1742 –

1832) in 1803. He observed at autopsy three specimens with narrowing of the spinal canal.28 He was also able to relate the pathological findings to the typical clinical symptoms of spinal stenosis.

The Italian orthopaedic surgeon Vittori Putti (1880 –1940), one of the most outstand- ing European orthopaedic surgeons of the first half of the 20th century, emphasised the relevance of anomalies or acquired degenerative alterations of the intervertebral foramina and lateral recess, for causing sciatica by causing an entrapment of the exiting root.28 In his article, published in The Lancet in 1927, Putti gained international attention and it was a further step in the understanding of the pathomechanism of sciatica in cases which are not caused by a slipped disc.29, 30, 31, 32 With the Dutch neuro- surgeon HenkVerbiest (1909–1997), also known as the “pope of spinal stenosis”, lumbar stenosis became a well-defined pathological entity.33He introduced the concept of developmental stenosis, which is caused by an abnormally short midsagittal diameter of the spinal canal.34, 35

Lane36, 37 in 1893 of England did a decompressive laminectomy to relieve a woman of cauda equina syndrome caused by spinal stenosis. Bailey and Casamajor38 wrote in 1911 that spinal nerve symptoms were caused by bone facet joint exotosis, which can cause significant compression of the spinal canal and cauda equina, and recom- mended laminectomy.

5 Review of Literature

Sarpyener39 in 1945 proposed the concept of congenital stricture of the spinal canal in his case series of 12 children who presented with both upper and lower motor neuron disease.

VanGelderen40 in 1948 proposed that a hypertrophied ligamentum flavum might result in spinal stenosis. He described two patients who showed signs of compression of the lumbar nerve roots with walking that disappeared with rest and were cured with laminectomy.

Verbiest 33, 41in 1954 defined the clinical syndrome of lumbar stenosis in seven patients who had bilateral radicular pain and motor and sensory disturbances in the legs caused by standing and walking. He described a myelographic block in the lumbar spine in every case, and at surgery a shallow canal with a compressed dural sac was observed. He postulated encroachment upon the canal by an enlarged articular process as a possible cause.

In 1978 Kirkaldy-Willis and colleagues42 studied the pathology and pathogenesis of lumbar spondylosis and stenosis and postulated that rotation and compression injuries led to degenerative changes of the three-joint complex. As a result of injuries, the intervertebral discs can develop circumferential or radial annular tears, internal disrup- tion, loss of disc height, and protrusion. The zygapophyseal joints can undergo synovitis, cartilage destruction, osteophyte formation, capsular laxity, ligamentum hypertrophy or buckling, and joint instability or subluxation.The results of these changes to the three-joint complex create degenerative spondylolisthesis, retrolisthesis, degenerative scoliosis, and rotational deformities.42

LUMBAR SPINAL CANAL STENOSIS:

6 Review of Literature

Spinal stenosis is a condition in which the spinal canal narrows and the nerve roots and spinal cord become compressed. Because not all patients with spinal narrowing develop symptoms, the term "spinal stenosis" actually refers to the symptoms of pain and not to the narrowing itself.43, 44, 45

Lumbar spinal canal stenosis is one of the most common spinal disorders in elderly patients, it may cause low back pain, radiculopathy and cauda equina syndrome.

Canal narrowing in part results from hypertrophy of ligamentum flavum, which mechanically compresses the nerve root or cauda equina.7 - 11

Lumbar spinal stenosis is narrowing of the central spinal canal, lateral recess or the neural foramen. The shape of the lumbar spinal canal varies and may be an oval, rounded triangular or trefoil configuration.46 The trefoil configuration usually occurs at the fifth lumbar level, making L4-L5 the narrowest level.47 And occurs in 25 % population, only appear- ing in adulthood.12 The anteroposterior diameter of the lumbar spinal canal is critical in the pathogenesis and is affected by the length of the pedicles.48

Fig. 1 Different shapes of spinal canal

7 Review of Literature

Wiltse in 1984 and Burton in 1987 included the intervertebral foramen in the nerve root canal, of which it is then the most distal portion. There are valid anatomical reasons for distinguishing between the two and identifying stenosis of the intervertebral foramen as a separate condition.49, 50, 51

Lumbar spinal stenosis is a progressive and dynamic process that causes narrowing of the spinal canal, lateral recess,or the neural foramina and is divided into two groups: congenital and acquired (Table 1). The narrowing results from the compression of the lumbosacral roots by the bony canal or the soft tissues, including the inter-vertebral discs, facet joints and the ligamentum flavum. This narrowing causes axial lumbar pain, radicular pain and cauda equina syndrome when the thecal sac and nerve roots are compressed,

90% of the population will report back pain, and the incidence of acquired lumbar stenosis is approximately 1 per 1000 in individuals older than 65 years.52, 53, 54

Table 1

Etiology of spinal stenosis

Congenital

Idiopathic Dwarfism

Achondroplasia

Morquio’s syndrome (mucopolysaccharidosis)

Hurler’s syndrome (mucopolysaccharidosis)

Acquired

Degenerative Spondylolisthesis

Scoliosis

Herniated/bulging intervertebral disc Lateral recess stenosis

8 Review of Literature

Facet hypertrophy

Neural foramen narrowing Ligamentum flavum hypertrophy Synovial cysts

Degenerative superimposed on congenital Spondylolytic (pars interarticularis defect)

Vertebral body compression fractures

Trauma

Metastatic disease

Spondylosis ankylopoetica (Bechterew’s disease) Iatrogenic

Postlaminectomy

Postfusion Tumors

Lymphoma

Meningioma Schwannoma Neurofibroma

Conus medullaris tumors

Myxopapillary ependymoma Pilocytic astrocytoma Hemangioblastoma

Miscellaneous/metabolic

Paget’s disease

Spinal epidural haematoma

Spinal epidural abscess

Diffuse interstitial skeletal hypertrophy

As life expectancy continues to increase, the prevalence of symptomatic spinal stenosis will increase. Although lumbar stenosis is not life threatening, it can cause chronic and substantial pain and can limit activity severely.55 Early and accurate diagnosis and treatment of lumbar stenosis important in preserving activity in the elderly population.55 Proper evaluation and treatment of lumbar stenosis requires knowledge of the anatomy and pathophysiology of the lumbar spine.56

9 Review of Literature

ANATOMY

The mobile, lordotic lumbar spine consists of five vertebrae and articulates with the rigid, kyphotic thoracic region superiorly and the rigid, kyphotic sacrococcygeal region inferiorly.

Lumbar vertebra: consists of a body, pedicles, lamina, pars interarticularis, transverse processes, spinous process, superior and inferior articular processes, and a neural foramen (Fig. 2).

Fig.2. Anatomy of the first lumbar vertebra. (A) Axial, (B) lateral, and (C) posterior views are shown. a - vertebral body; b- pedicle; c -vertebral canal; d- transverse process; e - superior articular process; f - lamina; g - spinous process; h -neural foramen; i - pars interarticularis; j - inferior articular process; k -mamil- lary process; l -accessory process. (P.B.Storm et al / Phys Med Rehabil Clin N Am 13 (2002) 713–733).

Intervertebral discs

10 Review of Literature

Intervertebral discs separate the vertebral bodies superiorly and inferiorly, and the articular processes form the zygapophyseal facet joint. Anterior and posterior longitudinal ligaments unite the vertebral bodies.57

Ligamentum flavum

The ligamentum flavum is a yellow, elastic tissue that forms the posterolateral wall of the vertebral canal. The ligamentum flavum spans the inferior edge of the lamina above and the superior edge of the lamina below.57

As the spine degenerates, there is a loss of intervertebral disc height, the inter laminar distance decreases, and the ligamentum flavum becomes hypertrophied, redundant, and occasionally, calcified. The redundancy worsens when the spine is in an erect position and particularly during extension.58

These changes in the ligamentum flavum can cause central stenosis by severely narrowing them in sagittal diameter of the lumbar spinal canal. The normal mid sagittal diameter of the lumbar vertebral canal is defined as greater than 12 mm.11, 59

Relative stenosis occurs when the canal diameter is between 10 and 12 mm, and absolute stenosis is defined as less than 10 mm.59, 60, 61

These measurements, however, are only guidelines. The extent of compression of the nerve roots and cauda equina and the patient’s signs and symptoms are more important than canal diameter.62

The intervertebral foramen has an inverted tear-drop or ear-shaped sagittal cross section and is more oval at the exit.62 The anterior wall of the foramen consists of the posterolateral aspect of the vertebrae and the intervertebral disc, respectively. The lig-

11 Review of Literature amentum flavum, the pars interarticularis of the upper vertebra and the superior articular facet of the lower vertebra form the posterior border of the foramen. The two adjacent pedicles form the upper and lower foramen borders. The foramen is mostly narrowed by osteophytes, decreasing disc height and foraminal disc protrusions.62

PATHOGENESIS

After initial recognition of spinal stenosis in 1802, a gradual understanding evolved over the next 150 years.63-66

It was Verbiest in 1976 who explained stenosis as ‘narrowing of the calibre of an ori- fice or tube. It causes a decreased flow of fluids or gasses within the tube or compression of its solid contents. In the case of the spinal canal, the term indicates a pathological condition causing compression of the contents of the canal, particularly the neural structures. If compression does not occur, the canal should be described as narrow but not stenotic.67

Franco Postacchini in 1983 defined lumbar spinal stenosis as a “narrowing of the osteo-ligamentous vertebral canal and/or the intervertebral foramina causing compression of the thecal sac and/or the caudal nerve roots; at a single vertebral level, narrowing may affect the whole canal or part of it”. This definition distinguishes between disc herniation and stenosis. A disc prolapse does cause stenosis, in the strictest sense, but the two conditions are so different in their pathogenesis and anatomical and clinical characteristics that they cannot be considered as a single pathological entity.67

12 Review of Literature

Harris and Macnab (1954) described the importance of disc degeneration in the pathogenesis of stenosis.67Macnab highlighted the lateral recess beneath the posterior facet joint.68

Verbiest identified neurogenic claudication as a result of spinal canal stenosis.69

A complete understanding of the pathologic anatomy of lumbar spinal stenosis is important to correlate the history, physical examination, and radiographic findings in assessing the patient with clinically symptomatic lumbar spinal stenosis.70

Spinal stenosis is a narrowing of the spinal canal by a combination of bone and soft tissues, which causes mechanical compression of spinal nerve roots. The compression of these nerve roots can be asymptomatic, but it can also become symptomatic, resulting in weakness, reflex alterations, gait disturbances, bowel or bladder dysfunction, motor and sensory changes, radicular pain or atypical leg pain, and neurogenic claudication. The term neurogenic claudication defines an intermittent pain or paresthesia in the legs brought on by walking and standing which is relieved by sitting or lying down.71-73

Lumbar spinal stenosis can be defined as any type of narrowing of the spinal canal, nerve root canals, or the intervertebral foramina.74

However, if compression of neural structures is absent, the canal should be described as narrow but not stenotic.75

The sequences of the progressive age-related changes which finally lead to the occurrence of a central or lateral stenosis have been nicely described by Kirkaldy- Willis.76 – 78

The pathomechanism of central spinal stenosis is predominantly related to a hypertrophy of the yellow ligament which is a result of a compensatory mechanism to destabilise a segmental hypermobility. Furthermore, bony canal compromise is caused by the occurrence of facet joint enlargement (osteoarthrosis), osteophyte formation,

13 Review of Literature and degenerative spondylolisthesis. This finally results in a progressive compression of the cauda equina. The majority of lateral recess stenosis is produced by disc height decrease, posterolateral disc protrusion or hypertrophy of the superior articular process. As a result of the degenerative changes with disc height loss, enlargement of the facet joints and foraminal disc herniation, the exiting nerve root is compressed.

Foraminal stenosis may also result from isthmic spondylolisthesis when the nerve root is compressed as a result of the olisthetic vertebra and disc height loss.79Lateral recess and foraminal stenosis are a common cause of lumbar radiculopathy.

Figure 3. Patho-morphology of central, lateral recess and foraminal stenosis

14 Review of Literature

Narrowing of the spinal canal can also be seen as a complication of metabolic disorders such as:

1. Diffuse idiopathic skeletal hyperostosis (DISH)

2. Paget’s disease

3.acromegaly

4. Hypoparathyroidism,

5. Pseudo hypoparathyroidism

6. X-linked hypo-phosphatemic osteomalacia

The anatomic presence of spinal stenosis is confirmed radiologically with computerized tomography (CT), myelography, or magnetic resonance (MR) imaging. The correlation of clinical symptoms with radiographic imaging is necessary to make the clinical diagnosis of lumbar spinal stenosis.80, 81

15 Review of Literature

Fig. 4 Normal and Stenotic vertebrae

Lumbar Canal Stenosis can be subdivided into 1) central stenosis 2) lateral stenosis.

Central stenosis

Central stenosis is found at the intervertebral level and is caused by ligamentum flavum buckling or hypertrophy, disc protrusion, hypertrophic zygapophyseal joints, and degenerative spondylolisthesis. Epidural fat is usually obliterated in the condition asideamount of posterior epidural fat, which may remain in the midline (Fig. 5).81

Fig. 5. Axial T1-weighted MR image demonstrating severe central stenosis secondary to disc bulge, ligamentum flavum hypertrophy, and zygapophyseal joint hypertrophy.

16 Review of Literature

The appearance of central stenosis on imaging studies is quite distinctive, with multiple levels usually involved. Imaging studies such as myelography and MR imaging can delineate these changes. Forty percent of central stenosis is secondary to soft tissue changes within the central canal.82

The cauda equina can be compressed centrally from an anterior-posterior direction at the intervertebral disc level. This compression may be caused either by a disc bulge or protrusion anteriorly or by hypertrophy and bulging of the ligamentum flavum associated with zygapophyseal joint hypertrophy, which can intrude posteriorly (Fig. 6).81 of posterior epidural fat, which may remain in the midline (Fig. 5).81

Fig. 6. Sagittal T2-weighted MR image demonstrating multilevel central stenosis from bulging discs (white arrows) and ligamentum flavum hypertrophy (white arrows).

The hypertrophy of the ligamentum flavum is known to be related to degenerative changes related to the aging process21, 83or mechanical stresses from instability.84, 85

17 Review of Literature

Morphologic and immuno histochemical studies have shown that the ligamentum flavum undergoes fibrotic and chondrometaplastic changes with aging.86

There is a proliferation of fibrocartilage (collagen type II), ossification, and calcium crystal deposition.21

A study by Park et al9 (2001) suggests that a higher expression of transforming growth factor-ß1 (TGF- ß1) by fibroblasts might be related to the development of hypertrophy of the ligamentum flavum. Hypertrophy of the ligamentum flavum has been described in anatomic studies to be 7 to 8 mm thick in patients with central stenosis, versus the usual 4 mm or less (Fig. 6).76

Fig. 7. Axial T1-weighted MR image demonstrating ligamentum flavum hypertrophy (white arrows) and disc bulge with resulting central spinal stenosis.

On imaging studies such as MR imaging or myelography there may be an apparent block of the cerebrospinal fluid around the cauda equina. On CT scanning, midsagittal lumbar canal diameters less than 10 mm are indicative of absolute stenosis, and diameters less than 13 mm are indicative of relative stenosis.34, 11

18 Review of Literature

The midsagittal lumbar canal diameters are not as reliable as the cross-sectional dimensions at the level of the intervertebral disc because most cases of degenerative spinal stenosis involve the lateral zygapophyseal joint soft tissues and discs, thus spar- ing the most central aspect of the canal.87

Schonstrom and Associate (1988)87 also believed there was poor correlation between the size of the bony canal and the size of the dural sac. They measured the cross-sectional area of the dural sac in stenotic patients using CT and found it to be

89.6 mm2 35.1 mm2, whereas in normal persons the area was 178 mm2, 50 mm2. They concluded that a constriction of the transverse area of the caudal equina to less than

75 mm2would cause pressure to increase around nerve roots and affect their normal function. They found that the pathologic determinants that resulted in the stenotic canal were ligamentum flavum hypertrophy, protruding discs, facet hypertrophy, lamina hypertrophy, and lysthesis. In developmental stenosis, a sagittal diameter of 12 mm seems to represent a border between normal and abnormal.34

In interpreting imaging modalities, one must remember that false-positive rates are high.88 - 90

Thus clinical findings must be used in correlation with the anatomic image to identify which patients are indeed presenting with clinical symptoms of lumbar spinal stenosis.

Patients with central spinal stenosis most commonly present with the clinical symptoms of neurogenic claudication.

Lateral stenosis

Lateral spinal stenosis is a common cause of lumbar radicular pain syndromes. The lateral lumbar spinal column includes the nerve root canal (lateral recess) and the

19 Review of Literature intervertebral foramen (neural foramen). These two areas together form a tubular canal through which the nerve root exits. The lateral lumbar spinal canal has been divided into three anatomic zones by Lee et al (1980)91: the entrance zone, mid zone, and exit zone (Fig. 8).

Fig. 8. Three zones of lateral stenosis: (1) entrance zone (lateral recess), (2) mid zone and (3) exit zone (intervertebral foramen). The entrance zone is the subarticular area and is medial to the pedicle. It is also synonymous with the term lateral recess area (Fig. 8). The midzone is located under the pars interarticularis and the pedicle. The exit zone is synonymous with the intervertebral foramen (neural foramen).

The entrance zone (lateral recess/subarticular area) is located anatomically underneath the superior articular process of the zygapophyseal joint and medial to the pedicle.

The entrance zone is the cephalad aspect of the more commonly known lateral recess that begins at the lateral aspect of the thecal sac and runs obliquely downward and laterally toward the intervertebral foramen.92, 93

20 Review of Literature

Anatomically, the lateral recess is bordered laterally by the pedicle, posteriorly by the superior articular process, and anteriorly by the posterior lateral surface of the vertebral body and adjacent intervertebral disc (Fig. 9)70

The medial border of the lateral recess is formed by the thecal sac.

Fig. 9 Entrance zone stenosis secondary to hypertrophy of the superior articular process with resultant compression of the nerve root on the right (arrow).

Hypertrophy of the superior articular process, particularly the medial border, may compress the nerve root between the facet and the dorsal aspect of the vertebral body. At this level the nerve root is covered by the root sleeve and is surrounded by cerebrospinal fluid. The lateral margin of the nerve root sleeve contacts the medial cortical bone of the pedicle, and the medial margin of the nerve root is surrounded by epidural fat tissue. Measurements of the normal lateral recess have been well delineated on computerised tomography.94

The height of the lateral recess equals the distance between the most anterior portion of the superior articular process and the posterior border of the spinal canal at the level of the superior margin of the corresponding pedicle.70

21 Review of Literature

A lateral recess height of 5 mm or more is normal. A height of 2 mm or less is pathologic, and a height of 3 to 4 mm is suggestive of lateral recess stenosis (Fig. 10).70

Fig. 10. Axial computerized tomography showing entrance zone (lateral recess) stenosis. The recesses (arrows) are visualized.

The most common cause for entry zone stenosis is hypertrophic osteoarthritis of the zygapophyseal joint, particularly involving the superior articular process. The other common cause of the narrowing of the entrance zone (lateral recess) is a posterior disc herniation, which compresses the nerve root as it emerges from the dural sac. These two causes account for most cases of lateral spinal stenosis. The mid zone is located under the pars interarticularis of the lamina and below the pedicle. The mid zone is bordered anteriorly by the posterior aspect of the vertebral body. The posterior border is the pars interarticularis, and the medial border is open to the central vertebral canal. The neural structures within the zone are the dorsal root ganglion and ventral motor nerve root, which are covered by a fibrous tissue extension of the dura matter. These neural structures are bathed in cerebrospinal fluid. The dorsal root ganglion occupies more space, because it is larger than other parts of the lumbar segmental nerves. Therefore in this

22 Review of Literature location it may be more sensitive to a lesser degree of stenosis. The midzone can be accurately imaged with CT scanning95 and also on sagittal MR imaging.96

In midzone stenosis, the most common cause of nerve root compression is a defect in the pars interarticularis. This defect can result from osteophyte formation under the pars interarticularis where the ligamentum flavum is attached or from a fibrocartilagi- nous or bursal tissue hypertrophy at a spondylolitic defect (Fig. 11).

Fig.11 (Left) Axial computerised tomography (CT) demonstrating a par defect with isthmic spondylolisthesis. (Right) Axial CT demonstrating the compression of the nerve roots from the par defect in the mid zone.

The second cause of nerve root compression in the midzone is pedicular kinking.

Pedicular kinking occurs when advanced intervertebral disc degeneration is associated with a marked narrowing of the disc; the vertebral bodies then approach one another.

As the upper vertebral body descends, its pedicle may, on occasion, kink the emerging nerve root to a significant degree (Fig.12)

23 Review of Literature

Fig. 12 Diagram depicting pedicular kinking of two lumbar nerve roots (left) versus two normal exiting nerve roots.

The nerve root could also be compressed in a gutter formed by a diffuse lateral bulge or protrusion of the intervertebral disc and the pedicle above. Pedicular kinking is most commonly seen with a L5-S1 spondylolisthesis.

This condition also occurs commonly in patients with scoliosis, which can result in one pedicle’s being lower than the other because of rotatory deformity of the vertebral body or asymmetrical collapse of the disc space.97

The third area in which lateral stenosis can occur is the exit zone (intervertebral or neural foramen). The lumbar intervertebral foramen is shaped like an inverted teardrop. Its superior border is formed by the posterior wall of the vertebral body above; the inferior border is formed by the posterior wall of the vertebrae below; and the posterior border is formed by the pars interarticularis, the ligamentum flavum, and the apex of the superior articular process of the interior vertebrae.17, 98

The normal foraminal height has been studied extensively by Hasegawa et al.

(1995)17 They found that the foraminal height, defined as the maximum distance between the inferior margin of the pedicle of the superior vertebra and the superior margin of the pedicle of the inferior vertebra, is between 17 and 23 mm. Foraminal widths were measured in an anterior-posterior width (horizontal plane). The normal width is

24 Review of Literature between 8 and 10 mm. A foraminal height of less than 15 mm and a width of less than

4 mm seem to be associated with nerve root compression 80% of the time.

Hasegawa et al 17 described nerve root compression as present when there was contact between the nerve root and the adjacent tissue. Deformation of the root was apparent- ly caused by pressure of the adjacent tissue. There was no perineural fat in the contact areas of the nerve root within the foramen in cadaveric studies. The largest structures within the intervertebral foramen are the dorsal root ganglia.

The dorsal root ganglia usually occupy the superior and lateral portion of the lumbar intervertebral foramen.99

The location can vary, however. Hasue et al (1989)100studied 83 cadaveric spines and reported that in 49 (59%) of these the L5 ganglia were in the intraforaminal region; in

27 (33%) the ganglia were in the intraspinal region; and in 7 (8%) the ganglia were in the extraforaminal region.

Common causes for exit zone stenosis are hypertrophic osteoarthritic changes in the zygapophyseal joints with subluxation and osteophytic ridge formation along the superior margin of the disc. A nerve root can be impinged upon vertically or horizontal- ly. This impingement can arise secondarily from subluxation of the superior articular facet, from a lateral herniated disc or protruding annulus, or from an uncinate spur from the posterolateral vertebral body. The intervertebral foramina can be well visu- alised on sagittal MR imaging scans. These images can show that the nerve root could be compressed or deformed by zygapophyseal joint subluxation, the ligamentum flavum, or a lateral herniated disc. The amount of absence of perineural fat signal on sagittal T1 MR images or the absence of space around the nerve visualized on CT scans can classify the severity of foraminal narrowing.101

25 Review of Literature

The lumbar spine is subjected to dynamic changes. The presence of lumbar stenosis when exposed to these daily forces should become more pronounced. Traditional non–weight-bearing imaging studies such as CT scans or MR imaging may not show the extent of these forces. Dynamic weight-bearing flexion and extension myelography may be best to evaluate these changes to the thecal sac diameter.102

The thecal sac diameter can be altered under axial loading, flexion, and extension moments.102 - 106

Cadaveric studies of normal lumbar spines by Schonstrom and colleagues105 demonstrated that narrowing of the cross-sectional area of the thecal sac occurred when the spine is placed in extension and axial compression.

Using dynamic myelography in a patient with neurogenic claudication, Dyck and

Doyle (1997)103found there was a free flow of contrast in weightbearing flexion, but in weight-bearing extension a high-grade partial obstruction was present.

Willen et al.106also evaluated the dynamic effects of axialcompression combined with extension of the lumbar spine in 84 patients using either CT myelography or MR imaging. They found that in 66 of 84 patients there was a statistically significant reduction of the dural sac cross-sectional area during axial compression and extension, and in 29 of these patients the cross-sectional area fell below the critical value for relative central stenosis. Furthermore, 9 of their 19 patients with disc herniation on MR imaging developed a corresponding radiculopathy with axial compression and extension.

Penning and Wilmink (1987)104have shown that flexion- extension myelography can identify the anterior displacement of the dural sac in extension along with concentric narrowing of the spinal canal. Thus, when observing a patient with mild to moderate

26 Review of Literature central or lateral stenosis, the dynamic forces on the lumbar spine must be clinically considered.

This review of the history, classification, and pathoanatomy of lumbar spinal stenosis is provided as a background for understanding a complicated condition affecting a multitude of patients. With a good understanding of the pathoanatomy of lumbar spinal stenosis, the clinician can correlate these anatomic findings to clinical symptoms to treat these patients appropriately and effectively.

Lumbar spinal stenosis results from changes in the three-joint complex.77, 107a tripod, with the disc as one leg and the facet joints as the other two legs, forming the posteri- or supports. Dysfunction in any of these joints leads to abnormal bio mechanical stresses that result in accelerated degeneration in the other joints and thereby create a cycle of degenerative changes. These degenerative changes cause central and lateral stenosis secondaryto remodelling andover growth of bone, with osteophyte formation, ligamentum flavum hypertrophy, facet hypertrophy, and disc bulging.108

Degeneration can begin at any of these sites, but disc degeneration seems to be the initiating event, with the articular processes affected secondarily.76, 77, 107, 108

As the disc degenerates and collapses, it can compress the thecal sac between a bulge in the annulus, encroaching on the vertebral canal anteriorly, and a hypertrophied ligamentum flavum, encroaching on the canal posteriorly.13

SIZE OF CANAL

In a normal-sized canal, degenerative discs usually do not cause symptoms of central stenosis; however, these degenerative changes superimposed on a congenitally narrowed canal can cause profound symptoms. A large disc herniation can compress the

27 Review of Literature thecal sac sufficiently to cause symptoms, regardless of canal size. This compression of nerve roots is especially true at higher lumbar levels, where the thecal sac has a similar diameter but a higher concentration of nerves.

Weisz and Lee (1983)109 used the term container content difference to describe this observation. Intervertebral discs contribute to lumbar stenosis not only by direct compression but also by increased mobility owing to loss of disc height, causing ligamentous laxity and accelerated degeneration of the facet joint.

The facet joint is a zygapophyseal joint composed of a descending inferior articular process from the vertebraaboveand the ascending superior articular process from the vertebra below. As the intervertebral disc loses height, increased stresses are placed on the facet joints, and the orientation of the facets begins to change (facet arthritis precedes disc degeneration in 20% of degenerative spines).110, 111

The increased mechanical stresses cause synovitis and cartilage erosion in the facet joint.112

As this process progresses, the joint undergoes arthritic and degenerative changes, and the facet capsule loosens, spinal motion increases, and further degeneration of the intervertebral disc and facet joint is accelerated. The increased spinal motion causes bone remodelling and overgrowth that lead toosteophyte formation and facet hypertrophy. Although osteophytes and hypertrophied facets reduce excessive joint motion by local physiologic arthrodesis (‘’autofusion’’), they also can narrow the canal, lateral recess, and neural foramina.113

Successful physiologic arthrodesis decreases segmental mobility at that level; however, the loss of mobility in one segment creates abnormal forces on adjacent levels that accelerate degenerative changes.108

28 Review of Literature

As the intervertebral discs narrow, the facets hypertrophy, and the ligaments weaken; there is a realignment of forces that can lead to degenerative spondylolisthesis.114

Spondylolisthesis is the anterior (anterolisthesis) or posterior (posterolisthesis) subluxation of the superior vertebral body relative to the subjacent one. Degenerative spondylolisthesis can not only cause narrowing of the vertebralcanal but also canpro- duce symptoms of spinal stenosis.115

Degenerative spondylolisthesis, however, should not be confused with isthmic spondylolisthesis.

In1976,Wiltseetal.116 classified spondylolisthesis into the following five categories: dysplastic (congenital), isthmic (spondylolitic), degenerative, traumatic, and pathologic. The two most common types of spondylolisthesis are isthmic (51%) and degenerative (25%).116, 117

Isthmic spondylolisthesis results from aneuralarchdefect causing alesionin the pars interarticularis, and it is the most common type of spondylolisthesis in patients younger than 50. Anterior isthmic spondylolisthesis occurs most commonly at the L5-

S1 level; however, degenerative anterolisthesis occurs almost invariably at the L4-5 level.117

The L5-S1 segment rarely has degenerative slips because the facets have a coronal orientation (L4-5 has a sagittal orientation), and the large transverse processes of L5 have strong ligamentous attachments to the iliac crest.118, 119

Degenerative spondylolisthesis can cause, or worsen, symptoms of stenosis because the anterior slip of the vertebra narrows the canal and compresses the thecal sac against the posterior body of the vertebra below. This condition usually occurs in a canal that is already stenotic from disc bulging, facet hypertrophy, and ligamentum

29 Review of Literature flavum hypertrophy. Symptoms of stenosis, however, are fewer with isthmic spondylolisthesis because the degree of slip is less and the compression of the thecal sac is minimal because of the neural arch defect.117

The chronic compression of the nerve roots of the cauda equina contributes to pain in lumbar stenosis. The mechanical deformation of the cauda equina causes venous con- gestion, ischemia, and axonal injury.120, 121

Chronic compression can induce radicular ischemia,122 sensitised nerve roots and dorsal root ganglia to inflammation123lead to Wallerian degeneration124 cause hyperalgesia, and release neurogenic pain mediators125, 126

Non- neuronal tissues important in stenosis (e.g., ligamentum flavum, intervertebral discs, facet joints) release endogenous chemicals that can produce pain.127, 128 These factors can combine to produce neurogenic claudication and multiple lumbar radiculopathies.Understanding the anatomyand pathophysiology of the lumbar spine allows physicians to study and consequently to diagnose and treat the clinical syndrome of lumbar stenosis more effectively.

The lumbar spinal stenosis is a clinical entity in which there is astrong correlation between symptoms and narrowing of the midsagittal diameter of the spinal canal, the lateral recess, and the neural foramina. The onset of symptoms is related to whether the stenosis is congenital (second or third decade) or acquired (sixth or seventh decade), but in either case, symptoms coincide with the development of osteoarthritis in a stenotic vertebral canal.129, 130

Degenerative spinal stenosis, the most common form of the disease, typically becomes symptomatic when patients are in their middle to late 50s or early 60s. 108, 131

30 Review of Literature

Degenerative lumbar spinal stenosis is three to five times more common in women than men, most commonly affects the L4-5 segment (followed by the L3-4 segment), and in approximately 5% of cases is associated with cervical stenosis.132, 133, 134

Degenerative spondylolisthesis is also five times more common inwomenand probably is related tohormonalfactors leading to ligamentous laxity.116, 135, 136

Patients typically present with insidious onset of chronic low back pain that progresses to coccygeal, gluteal, thigh, and leg pain.137

The quality of the axial back pain in lumbar stenosis is the ache and stiffness of osteoarthritis; activity exacerbates the pain, and rest relieves it.71

Patients often report limitations during spinal extension but not during flexion. Exten- sion frequently causes severeand lancinating paininto the buttocksand lower extremities. Patients often report that they are able to relieve their pain by sitting downandflexing their low back. The lower extremity pain associated with lumbar spinal stenosis is dependent on the area of stenosis and is characterized by the syndrome of neurogenic claudication. This syndrome is characterized by poorly localised pain, numbness, paresthesias, weakness, and cramping or burning in the low back, buttocks, and lower.76, 138

The pain typically radiates from the low back or buttocks into the thigh and knee in a radicular pattern. As activity increases or the condition progresses, the leg and foot may become involved.131

Walkingorstanding exacerbates symptoms,whereas sittingor lying with the hipsand spine flexed substantially alleviates the pain.139

Because flexion relieves discomfort, many patients with stenosis ambulate with as- toopedposture.108

31 Review of Literature

Patients often can increase walking tolerance when leaning forward over a shopping cart (‘‘shopping-cart sign’’), lawn mower,or while walking uphill.This postureflexes the lumbar spine and widens the inter laminar distance, thereby decreasing the redundancy of the hypertrophied ligamentum flavum and reducing the compression on the cauda equina. The opposite is true of postures that increase lumbar lordosis, such as sleeping, which explains why many patients report worsening of symptoms in the middle of the night or early in the morning. As the stenosis progresses, rest pain may develop, postural changes may no longer relieve pain, and a neurogenic bladder may develop; however, patients with lumbar stenosis rarely present with a cauda equina syndrome.138, 139

The diagnosis most often confused with neurogenic claudication is vascular claudication from peripheral vascular disease (Table 2).140

Table 2

Neurogenic vs. vascular claudication

Signs and symptoms Neurogenic claudication Vascular claudication

Painonliftingorbending Common UnCommon Claudicatingdistance Variable Constant Pain distribution Distribution of a nerve Distribution of a muscle

(dermatomal) group (sclerotomal) Pain relief Sittingorflexedposture Not dependent on posture

Standingandresting Reliefwhilestanding

usually insufficient Pain Pain relief is almost im-

relief is often slow mediate

(>5–10 min)

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Bicycle ride No pain Pain Qualityofpainsensation Achingandnumb Crampingandtight Peripheral pulses Present Absent or diminished

Ankle/brachial pressure > 0.95 <0.95 (typically closer to index 0.7) Atrophy Rare Present

Back pain Common Uncommon

Skin Normal Alopetic, shiny

The main difference is the absence of low back pain in vascular claudication. Claudi- cation caused by peripheral vascular disease is characterized by cramping pain or tightness that begins in the calves and progresses proximally (neurogenic claudication begins proximally and progresses distally) and reproducibly occurs at a constant distance. The pain of vascular claudication improves with standingandis exacerbated by lying.Having the patient ride a stationary bicycle is an excellent way to define the type of claudication; patients with vascular claudication should become symptomatic, but patients with neurogenic claudication should tolerate the exercise because their lumbar spine is flexed. Patients with vascular claudication more commonly have diabetes mellitus, smoke cigarettes, have decreased dorsalis pedis and posterior tibialis pulses, have cutaneous changes over the distal lower extremities, and have an ankle/ brachial pressure index of 0.7.141, 142

These two conditions, however,can exist simultaneously,making the correctdiagnosis difficult and possibly requiring consultation with avascularsurgeon to determine the best treatment.

33 Review of Literature

Other conditions in the differential diagnosis include herniated discs and peripheral neuropathy. Herniated discs typically occur in a younger population, and the onset of symptoms is usually sudden. For example, sudden onset of acaudaequinasyndrome

(discussed ina following section) resulting from a large herniated discis different from the insidious onset of a cauda equina syndrome from spinal stenosis. Peripheral neuropathy can be confused with lumbar spinal stenosis in an elderly person. Patients with peripheral neuropathy, however, typically have diabetes and report a burning sensationin their feet that progresses proximally. These symptoms are unrelated toac- tivityandoccurinastocking distribution.143

Itis important to rule out osteoarthritis of the hips, tumours at the conus medullaris, metastatic disease to the spine, infections, and fractures. A careful history allows the physician to make the diagnosis of lumbar stenosis in most cases; however, physical examination is extremely important to confirm the diagnosis of stenosis and rule out other conditions in the differential diagnosis.

Physical examination of the back may show a loss of lordosis of the lumbar spine, but palpation usually does not produce tenderness. The most common finding inl um- barstenosisisabsence of the ankle (gastrocnemius/soleus) deep tendon reflexes.

Range-of-motion manoeuvres demonstrate that forward flexion is decreased but pain- less, and that extension is restricted severely and may cause pain into the buttocks and lower extremities. Straight leg–raise (SLR) testing results are usually negative but may be positive, depending on the extent of lateral recess stenosis.48

Straight leg–raising (SLR) results are much more likely to be positive in younger patients with a disc herniation. Motortestingis usually normalorreveals,at worst, only a minimal loss of function.48, 135

34 Review of Literature

If weakness is present, it is usually mild and involves the extensor hallucis longus or tibialis anterior because the L4-5 level and L5 root are affected most frequently. Atrophy in the thigh or leg is uncommon but canexistin the presence of long-standing compression.

Ciric et al. (1980)144 found a higher correlation between weakness and atrophy in patients with lateral recess stenosis compared with patients with central stenosis only.

Cauda equina syndrome

The distal spinal cord terminates at the L1-2 level in a diamond-shaped enlargement called the conus medullaris. The lower motor and sensory nerve roots exit the conus medullaris and form the cauda equina (‘‘horse’s tail’’) in the thecal sac.145, 146

Compression of the lumbosacral nerve roots located in the thecal sac may produce multiple unilateral or bilateral radicular signs and symptoms diagnosed as cauda equina syndrome (CES).147

There are multiple compressive causes of CES, including herniated lumbar intervertebral discs, spinal stenosis, trauma, chiropractic manipulation, and spinal neoplasms.147, 148

Non compressive causes also must be considered in the differential diagnosis and include ischemic injury, inflammatory conditions, spinal arachnoiditis, and infections.147

The classic clinical presentation of CES is characterized by low back pain, bilateral sciatica, and saddle anaesthesia, weakness of the lower extremities that may progress to paraplegia, bowel and bladder dysfunction, and impairment of the bulbocavernous, medio- plantar, and Achilles tendon reflexes.147, 149, 150

These signs and symptoms are typically bilateral but may be asymmetric.149

Although evaluating a patient with back pain who presents with ‘‘classic’’CES typically does not represent a diagnostic challenge, evaluating a patient with back pain

35 Review of Literature who has early and incomplete signs and symptoms of CES is a difficult problem.

Back pain is a common complaint that affects up to 90% of the general population at some time in life, and most have complete resolution of symptoms by 4 weeks.151, 152

Because most back pain is benign, early CES often goes undiagnosed.

In 1999, Kennedy et al.153 published a retrospective review of 19 patients with CES.

They found that all patients had saddle hypoaesthesia and bladder dysfunction. The group with a satisfactory outcome had a mean time from onset of symptoms to decompression of 14 hours (range, 6–24 hours), but the group with a poor outcome had a mean time of 30 hours (range, 20–72 hours).

There ismuchconfusion among physicians about‘‘urinaryincontinence’’associated with spinal cord compression and CES. Patients with spinal cord compression and

CES develop urinary retention initially, and only later do they develop overflow incontinence. Many patients deny urinary ‘‘incontinence’’but may have large urine vol- umes in their bladder on post-void residual testing. Therefore, it is imperative to check a post-void residual test if there is the slightest suspicion of CES.

Deyo et al. (1992)154 report that the finding of urinary retentionhasasensitivity of

90%anda specificity of 95%in CES. They also report that the absence of a large post- void residual essentially rules out CES, with a negative predictive value of 99.9%. We do not recommend, however, relying solelyon the post-voidresidualtesttomake the diagnosis of CES when evaluating back pain. Instead, we recommend careful history taking and physical examination, with anemphasison perineal sensation, rectal tone, and measurement of post-void residual for proper and early diagnosis of CES as well as early and prompt surgical decompression.

Diagnostic workup

36 Review of Literature

After a careful history is taken and a physical examination is performed, the diagnosis of lumbar stenosis is confirmed by radiographic studies. Electrodiagnostic studies of the lower extremity are rarely necessary because the diagnosis is established clearly by the history, examination, and most importantly, the radiographic studies.

Imaging

The most important radiographic studies (Fig.12) for evaluating lumbar stenosis are MRI,

CT, and rarely, CT myelography. Plain lumbosacral radiographs, including flexion/ extension views, always are obtained. In most instances of lumbar stenosis, these techniques not only have similar accuracy rates but also are often complementary; however, they all have advantages and disadvantages, depending on the source of the stenosis.155, 156

Because all of these treatment modalities can diagnose lumbar stenosis adequately,

MRI is the initial study of choice because it does not use ionizing radiation or require contrast injection.157

Plain lumbosacral radiographs that include flexion/extension views are also an inte- gral component of the radiographic workup. These radiographs provide an estimation of the degree of mechanical instability, which may necessitate supplementing the surgical decompression with a fusion.

MRIisanoninvasive study that isoutstandingfor delineating hypertrophied ligamenta flava, bulging discs, compressed nerve roots, dural sac impingement, lateral recess stenosis, and narrowed neural foramina. It provides both sagittal and axial images of the spine. MRI, however, tends to under-represent bony abnormalities such as hypertrophied facets and spondylolisthesis, and it is not as reliable as CT for this purpose. other disadvantages of

MRI are that patients with ferromagnetic implants cannot be scanned and that even MRI- compatible metallic implants generate significant scatter artifact.

37 Review of Literature

Fig. 13. A 67-year-old man with neurogenic claudication and a left L4 radiculopathy. (A) Midline sagittal T2-weighted image showing a bulging degenerative disc (arrow) at L4-5 and thickening of the ligamentum flavum (arrowhead).(B) SagittalT2 weighted image of the left neural foramina. The hypointen- sity of the L4-5 neural foramen, which is traversed by the L4 nerve root, represents soft tissue in the foramen (arrow). The neural foramina at the other levels are normal. (C) Axial T2-weighted image showing the bulging disc (arrow) and thickened ligamentum flavum (arrowhead). (D)Axial CTscan showing lateralrecess stenosis (arrows)and extensive facet hypertrophy (arrowheads). CT is a non invasive study that isbetter than MRI at defining bony abnormalities and also is less expensive. Unfortunately, CT scans do not provide the soft tissue information seen on MRI and use ionizing radiation to generate images. CT myelography is an invasive study that gives excellent soft tissue and bony definition, but it is used less frequently because it requires the injection of dyeandusesionizing radiation.The soft tissue resolution of MRI is superior. CT myelography is the study of choice,

38 Review of Literature however, when the patient has had prior surgery either with or without instrumentation.157

Even though the resolution of CT and MRI provides invaluable detail, it is important not to underestimate the importance of plain radiographs. Plain films provide excel- lentbony detail,illustrating fractures,osteophytes, hypertrophied facets, spondylolisthesis, pars interarticularis fractures, disc degeneration, spinous process settling

(‘‘kissing spines’’), narrowing of the interpediculate distance, scoliosis, and metastatic disease. As already mentioned, flexion/extension lateral views areusefulindetermining the extent to which translational or angular mobility occurs at a potentially unstable segment. In the authors’practice, it is routine for all patients who are being operated on to have plain films in addition to MRI or CT scans.

Electrodiagnosis

Electrodiagnostic testing consists of electromyography (EMG), nerve conduction velocities, and somatosensory-evoked potentials. As imaging techniques have improved, electrodiagnostic testing is no longer used routinely in the workup of spinal stenosis, but there are instances when it may help the physician make the diagnosis of neurodegenerative or neuromuscular conditions resemblingspinalstenosis.For example, apatient whose history and physical examination findings are suggestive of lumbar spinal stenosis but also areaccompaniedbyanMRI that does notshow narrowing should undergo electrodiagnostic testing. The three major electrodiagnostic tests are discussed briefly.

Electromyography

Electromyography evaluates the physiology of lower motor neurons. It does not evaluate sensory abnormalities or upper motor neuron disturbances. If the nerve supply to

39 Review of Literature a muscle is damaged by disease of the ventral horn cell, nerve root, or peripheral nerve, the muscle is ‘‘denervated’’and has a typical pattern on EMG.158

Electromyographs of patients with spinal stenosis often show bilateral multi radicular abnormalities, even if the patient’s symptoms are not bilateral.159

In patients with a complete myelographic block, 87.5% had bilateral EMG changes, whereas 29% of patients had bilateral EMG changes when their myelogram was normal.160 because symptoms of spinal stenosis are predominantly sensory and EMG evaluates motor neurons, it is not uncommon to have a normal EMG. Electromyo- graphic findings do not predict surgical outcome,161 and EMG alone should not be used to determine the levels of decompression.

Nerve conduction velocities

Electromyography measures the effect of a nerve on a muscle, but it does not provide information on the speed at which the nerve impulse travels. Nerve conduction veloci- ty is a test that accurately determines the time taken for an impulse to traverse a measured length of nerve and reports the values in meterspersecond.Itisausefultestfor dif- ferentiating peripheral neuropathy from radiculopathy.162

Somatosensory-evoked potentials

Somatosensory-evoked potentials are transmitted through the dorsal columns and measure the sensory component of the nerve. Lesions of peripheral nerves prolong the latency response. Although somatosensory-evoked potentials have been used to evaluate stenosis because they measure the sensory component of the nerve, their greatest use has been for intra operativemonitoring.163

Natural history

40 Review of Literature

The natural history of degenerative lumbar spinal stenosis is not well understood.

Soon after Verbiest made lumbar stenosis a recognisable clinical entity, neurologic and orthopaedic surgeons believed that spinal stenosis was a degenerative and progressive disease that narrowed the canal, caused symptoms, and required surgical decompression to break the cycle of instability leading to more stenosis.116, 164, 165, 166

Asaresult,most literature concentrated on the surgical outcome, and little is known about nonoperative treatments.

Clinical data and experience, however, now suggest that even though most lumbar spinal stenosis is degenerative, it is not necessarily progressive, and surgical treatment can be avoided.167, 168

Several studies report that many patients with mild to moderate stenosis do well without surgery.168, 169, 170

These studies emphasise that patients with radiographic and clinical lumbar spinal stenosis can have improvement by properly tailoring non-operative treatment. For example, strength training, weight loss, stretching, and cardiovascular training may improve circulation to the cauda equina and decrease the severity of neurogenic claudication. Treatment with anti- inflammatory medications can decrease the radicular pain associated with lumbar stenosis. 171

These therapies mayameliorate symptoms long enough for the spine to undergo physiologic arthrodesis or for pain fibers to adapt to compression and no longer cause pain. These changes could result in long-term symptomatic relief.

As a result of reports of patients who do well without surgery, investigators began comparing surgical and nonsurgical outcomes.

41 Review of Literature

Johnsson et al. (1995)165found that 60% of the patients treated surgically improved and 25% deteriorated. Of the conservatively treated patients, 30% improved and 60% were unchanged.

In a separate study in 1992, Johnsson et al.165examined the natural course of spinal stenosis. The study reported on 32 patients followed up non operatively for an average of 49 months and found that 15% had improvement in their symptoms, 70% were the same, and 15% were worse. The authors could find no evidence of deterioration at

4 years, and they concluded that expectant observation could be an alternative to surgical treatment because of the slow progression of degenerative lumbar stenosis.

In 2000, Amundsen et al. (2000)171 performed a prospective, randomised study of

100 patients, with a 10-year follow-up period, to identify the short- and long-term results after conservative and surgical management. They found that after 3 months, pain relief had occurred in most patients. After 4 years, excellent or fair results were found in 50% of the patients selected for conservative treatment and in 80% of the patients selected for surgery. They also found that patients who had unsatisfactory results from conservative treatment and then underwent delayed surgery had the same results as patients initially randomly assigned into the surgery group. Taken together, the study of Amundsen et al.171and other studies171, 172, 173, 168, 169 suggest that conservative treatment is advocated in patients with mild to moderate symptoms of lumbar stenosis and that surgical treatment is indicated in patients with severe symptoms. Of note, however, is that important variables such as psychosocial factors, depression, anxiety, litigation, workmen’s compensation, and general patient health and fitness often are not assessed and can have a significant effect on outcomes.

42 Review of Literature

Patients who fail to improve with conservative therapy and have clinical and radiographic evidence of lumbar stenosis are candidates for surgical decompression. One of the risks associated with a decompressive laminectomy is the development of secondary spinal instability—instability that occurs after lumbar surgery (primary spinal instability occurs de novo and results from trauma, infection, or neoplasm and degenerative disorders of the spine.174

An overzealous bony decompression that removes one facet joint or more than 50% of both facet joints and that sacrifices the pars interarticularis is likely to lead to instability.175

Lumbar ‘‘instability’’is a common diagnosis of severe back pain and disability and is treated with a fusion procedure; however, there is no clear consensus of what consti- tutes‘instability.’’175 The lack of consensus among physicians regarding the definition of instability makes collecting data difficult and developing evidence-based indications forfusion even more difficult.

In1995, Sonntagetal. 175 published three different grades of pathology (recommend- ed, relative, and rare) warranting spinal fusion. Stable spinal stenosis and grade I spondylolisthesis are listed in the ‘‘rare’’category. Obviously, several medical and psychologic factors must be considered, regardless of the pathology, before a patient is considered for a fusion. This consideration is especially necessary for elderly patients.

It is of concern that the rates of lumbar fusion procedures are increasing rapidly, especially for lumbar stenosis in the elderly.176

In 1995, Katz175 reviewed the spinal fusion literature and found that fusion rates var- ied markedly among individual surgeons and geographic regions. He also found that

43 Review of Literature fusion for spinal stenosis was associated with higher costs and complication rates than decompressive surgery without fusion. The spines of the elderly have often physiolog- ically auto fused and tolerate a generous decompression without causing or exacerbat- ing a spondylolisthesis.108, 177

Because of the increased morbidity associated with lumbar fusion in the elderly and the fact that the rigid elderly spine has decreased mobility, the authors rarely perform a fusion in patients more than 60 years old during the initial decompression for spinal stenosis. Younger patients are more difficult to manage because they still have mobile spinal segments that can cause or exacerbate a spondylolisthesis and cause pain, they have fewer comorbidities, and they do not tolerate an extensive decompression as well as elderly patients. The authors still prefer, however, to avoid a fusion, but the threshold to fuse at the initial decompression is lower in patients younger than 50.

When a fusion is necessary, the authors generally favour an in situ fusion of the facet joints over one with instrumentation.178

A prospective study by Katz et al. (1999)177 to identify outcome predictors of surgery for degenerative lumbar stenosis found that the patient’s assessments of his or her own health and comorbidity are the most cogent outcome predictors. The study also found that low cardiovascular comorbidity predicted a favourable outcome. Although outcome predictors for conservative management were not examined, it is likely that low cardiovascular comorbidity similarly would predict a favourable outcome on nonoperative management. An important component of nonoperative therapy consists of therapeutic exercise.179, 180

A healthy cardiovascular system would allow patients to tolerate the stretching and strengthening programs of conservative therapy.

44 Review of Literature

More prospective, randomised studies with valid and reliable outcome measures are required forbetterunderstanding of the natural history of lumbar stenosis and indications for conservative and surgical treatment. Indeed, additional clinical and experimental work is needed to elucidate the myriad causes of pain in the stenotic lumbar spine. This knowledge will provide new and improved treatment options for patients with low back pain.

SPINAL LIGAMENTS (White and Panjabi 1990)180

Excluding the upper cervical spine, a FSU is connected by 10 ligaments, which serve to protect neural structures by restricting the motion of each FSU. The ligaments also absorb energy during high speed and potentially injurious motions. The spinal ligaments are primarily collagenous except for the ligamentum flavum, which is primarily comprised of elastin.

The anterior longitudinal ligament (ALL) originates at the base of the occiput and extends the entire length of the spine into the sacral region along the anterior aspect of the spine.

Fibers of the ALL firmly attach to each vertebra, as well as to the intervertebral disc.

The posterior longitudinal ligament (PLL) also extends the length of the spine along the posterior aspect of each vertebral body and anterior to the spinal cord.

The ligamentum flavum (LF) originates bilaterally on the anteroinferior aspect of the lamina of the superior vertebral body and inserts on the posterosuperior aspect of the lamina of the inferior vertebra.

The intertransverse ligaments (ITL) and interspinous ligaments (ISL) join transverse and spinous processes, respectfully, of adjacent vertebrae. The supraspinous ligament (SSL) originates as the ligamentum nuchae (LN) of the neck and extends the length of the spine posterior to the ISL, while attaching firmly to the tip of each spinous process.

45 Review of Literature

The capsular ligaments (CL) surround each facet joint.

Mechanically, spinal ligaments behave as other soft tissues of the body: they are viscoelastic with nonlinear elastic responses. Their mechanical response has been characterized predominantly ex vivo (cadaveric tissue outside the living body) and little is known about their in vivo (within the living body) mechanical environment. In general, it is believed that spinal ligaments do not enjoy the same margin of safety as bones do, as they can operate under conditions relatively close to their failure strengths.181

Fig. 14 Lumbar Ligamentum Flavum Hypertrophy

LUMBAR LIGAMENTUM FLAVUM HYPERTROPHY

No one knows exactly why the ligamentum thickens in some patients and not others.

As we age, it is normal to experience some hypertrophic change in this structure, but in other cases, the source is deemed to be the result of a spinal abnormality or spinal injury. In many cases, the cause is idiopathic, as is common with some many back pain conditions.182

46 Review of Literature

The most common spinal disorder in elderly patients is lumbar spinal canal stenosis causing low back and leg pain and paresis. Canal narrowing, in part, results from hypertrophy of the ligamentum flavum. Although histologic and biologic literature on this topic is available, the pathomechanism of ligamentum flavum hypertrophy is still unknown.183

Elsberg CA. (1913)8first hypothesized that the ligamentum flavum, which envelops the medial aspect of the facet joints, is thought to play a role in spinal disorders, when he noted that a torn ligamentum flavum can “compress the fourth lumbar root”. 7

Since then, others have suggested that the ligamentum flavum plays an important role in the spinal disease, most prominently spinal stenosis.8-11

The ligamentum flavum (LF) is a yellow elastic ligament extending from the second cervical vertebra to the first sacral one.LF thickness is an age-dependent and gender- independent phenomenon.The LF connects 2 adjacent laminae and lines an important part of the osseous and soft tissue sections of the posterior epidural region.23,182, 183, 185, 186

J Abbas et. al (2010)187 noted that Ligamentum flavum bulges inside the spinal canal or foramen at the extension position of the lumbar spine and compresses nerve tissues.LF lines a considerable part of the posterior and lateral walls of the spinal canal and is a major role contributor to the spinal canal stenosis.9, 12, 21, 84, 85, 187, 188

In 1969 Verbiest identified neurogenic claudication as a result of spinal canal stenosis.69

47 Review of Literature

LF lines a considerable part of the posterior and lateral walls of the spinal canal and is a major role contributor to the spinal canal stenosis.One of the reason may be the change in the thickness of the ligament, accompanied by distance shortening between adjacent vertebral arches. 14, 15, 16, 23, 189

Furthermore, there is a report that foraminal stenosis occurs due to degenerative changes of the lumbar spine, such as a decrease in disc height and volume redistribution of the ligamentum flavum involves nerve compression inside the foramen.190, 191, 192, 193, 194

The ligamentum flavum attaches to the ventral side of the vertebral arch and makes up the posterior wall of the spinal canal or foramen. Thus, it is considered to be one of the important factors in the causes of radiculopathy or cauda equina symptoms in lumbar degenerative disease.14, 15, 16

One of the reasons may be the change in thickness of the ligament, accompanied by distance shortening between the adjacent vertebral arches.23.

48 Review of Literature

One of the reasons may be the change in thickness of the ligament, accompanied by distance shortening between the adjacent vertebral arches.23

Furthermore, there is a report that foraminal stenosis occurs due to degenerative changes of the lumbar spine, such as a decrease in disc height17, 24 25, 26, 27 and volume redistribution of the ligamentum flavum involves nerve compression inside of the foramen.27

Thus, the morphological changes of the ligamentum flavum that are due to the change of lumbar spine alignment, as well as a decrease in disc height associated with degeneration, may result in compression on nervetissues. There have been several reports anatomically examining the positional relationship between the ligamentum flavum and dura or nerve root 195, 196, 197 but there are few reports on ventral observation 198 and no reports describe the morphological changes of the ventral side of the ligament accompanied by lumbar spine degeneration. Furthermore, when the ligamentum flavum is resected via a dorsal approach76 the overall picture of the ligamentum flavum cannot be seen from the dorsal side. Consequently, some of the hypertrophied ligamentum flavum may remain un-resected, which may lead to recurrence due to lack of decompression.199

Teruaki Okuda et. al (2005)200concluded in their study that from the ventral side, they were successful in observing the surface where the ligamentum flavum actually contacts the nerves three-dimensionally. Therefore, they could more realistically grasp the relationship between the swollen morphology of the ligamentum flavum and nerve root compression, which has until now been difficult to imagine.

49 Review of Literature anatomically examining the positional relationship between the ligamentum flavum and dura or nerve root195, 196, 197but there are few reports on ventral observation198 and no reports describe the morphological changes of the ventral side of the ligament accompanied by lumbar spine degeneration. Furthermore, when the ligamentum flavum is resected via a dorsal approach.76, 199

The overall picture of the ligamentum flavum cannot be seen from the dorsal side.

Consequently, some of the hypertrophied ligamentum flavum may remain un-resected, which may lead to recurrence due to lack of decompression.200

Postacchini F et al (1994)201 studied the ligamenta flava from patients with lumbar stenosis showed areas of fibrosis in which the cells were often represented by actively synthesizing fibroblasts and areas of chondroid metaplasia. Degenerating elastic fibers were seen occasionally, while calcified areas were observed often.

Also the Ligamenta flava undergo slight fibrotic and chondrometaplastic changes with aging. No peculiar changes occur in patients with disc herniation. In spinal stenosis, fibrotic changes, chondroid metaplasia, and calcification reduce the elasticity of the ligaments, which may thus bulge into the spinal canal in the standing position even if they are normal in thickness.202

Hidden Zone:

In performing lateral fenestration for lesions in the foraminal zone, such as extreme lateral lumbar disc herniation, 203, 204 it is difficult to determine decompression range, because the location and shape of the attachment portion of the ligamentum flavum inside of the foramen, or the structure between the transverse processes, are not clear.

This area is named the ‘‘hidden zone’’by Macnab (1971).203

50 Review of Literature

Furthermore, with respect to the extraforaminal zone, the most exterior area, Wiltse

(1984)205 called this the ‘‘far-out zone’’and reported that the L5 nerve root was compressed between the L5 transverse process and the superior portion of the medial sacral ala at the L5–S1 level. However, there are few detailed reports regarding the structure outside of the foramen.206, 207, 208, 209 so anatomical image in the far-out zone is difficult to grasp.

Teruaki Okuda et. al (Eur Spine J 2005)200 concluded that shape of the ligamentum flavum seen ventrally was not uniform and had changes including bulge, erosion, fold, and bone exposure. The relationship between these morphological changes of the ligamentum flavum and radiographic findings was examined, and a significant correlation between the proximal bulging type and a decrease in disc height was found.

A possibility was reported that disc collapse associated with disc degeneration led to a decrease in intervertebral height and frequently buckled the thickened ligamentum flavum 21, 209

Why proximal bulging occurs:

(1) A decrease in disc height leads to shortening of the distance between the vertebral arches and thickening of the interlaminar portion of the ligament, while the superior articular process moves to the cranial side, causing infolding in the capsular portion of the ligament.17, 24, 25, 26

As this mechanism, Rauschning27mentioned involvement of a secondary volume redistribution of the ligamentum flavum, due to a decrease in disc height.

(2) In the ligamentum flavum of the proximal bulging type, the distal side of the ligament is in contact with the disc and forms depression at that site. Thus, the annulus fibrosus bulges posteriorly in association with a decrease in disc height and com-

51 Review of Literature press the distal side of the ligamentum flavum facing the annulus fibrosus. This causes the cranial portion covering from the subarticular zone to the foraminal zone to bulge like a boomerang. With the whole bulging type, the intervertebral angle tends to be great, which may be caused mainly by shortening of the interlaminar portion of the ligament, due to a large amount of anterior dilatation of the interbody17, 18, 20, 2, 22, 23,

26The nerve roots in the foraminal zone became vulnerable to compression.17

Therefore, in patients who clinically complain of lumbar radiculopathy symptoms, with a decrease in disc height on lumbar radiographs, the ligamentum flavum that bulges in the proximal portion from the subarticular zone to the foraminal zone is potentially compressing the nerve root. Thus, surgeons should remember that the nerve root may be compressed by bulging ligament in these zones.210, 211

Kyung Hyun Kim et al. (2013)212 observed in their study that spinal canal diameters in the LSS group were significantly lower than in the control group at both the largest movable (L4-5) and least movable segments (T5-6), similar to the study reported recently by Abbas J et al.187 However they showed how the spinal canal diameter changes with age in LSS. They found that aging did not affect bony spinal canal diameters in either LSS or controls. Therefore, the narrow bony spinal canal in LSS is not due to aging, but rather genetics.

Masharawi and Salame213reported that age is not associated with spinal canal width and length variation in the thoracic and lumbar vertebrae in normal people.

Hirofumi Kosaka, Koichi Sairyo et. al (2007)214in their histologic study showed that the normal layer, which includes a lot of elastic fibers, was also hypertrophied. The expression of elastin mRNA in LF cells showed a positive linear correlation with age, suggesting that LF in the elderly may produce large amounts of the elastic fibers as

52 Review of Literature compared with LF in the young generation. These histologic and biologic results could propose that LF hypertrophy may be due to the thickening of the normal elastic layer as well as of the abnormal collagenous layer. They concluded thatdecreased elasticity of LF in the elderly is due to the loss of elastic fibers and a concomitant increase of collagenous fibers in the dorsal aspect. LF hypertrophy could be due to the thickening of the normal elastic layer as well as of the abnormal collagenous layer.

Koichi Sairyoet. al (2007)215proposed the following hypothesis for the pathomechanism of ligamentum flavum hypertrophy. Mechanical stress-induced tissue damage, especially on the dorsal side of ligamentum flavum, would be the initial triggering event. Then, an inflammatory reaction would occur, and tissue scarring would develop. Accumulation of the scar would result in ligamentum flavum hypertrophy. Some growth factors such as TGF-ß1 may also play a role in this pathway. Finally, due to the interplay of inflammation, injury, scar formation, and similar observations in other soft tissues (e.g., knee ligaments), our data for the first time suggest that the drug therapy may help reduce/control ligamentum flavum hypertrophy.

Koichi Sairyo et al. (2005)216suggested that fibrosis is the main cause of ligamentum flavum hypertrophy, and fibrosis is caused by the accumulation of mechanical stress with the aging process, especially along the dorsal aspect of the ligamentum flavum.

TGF-ß1 released by the endothelial cells may stimulate fibrosis, especially during the early phase of hypertrophy.

MarcelO Ferraz de campos et. al (2014) 217 evaluated the expression of matrix metalloproteinases and TGF-ß1 in patients with spinal stenosis and in younger patients who have herniated disc.There was an increase in TGF-ß1 in older individuals, although without statistical significance. The metalloproteinases did not present any

53 Review of Literature significant differences between the groups, either in relation to age, or to the type of alteration in the spine.

Luiz Claudioet al.(2014)218concluded that the use of oral corticoids is not effective in the treatment of lumbar canal stenosis. Obese patients with lumbar canal stenosis show more pain or poor function and quality of life.

Shoji Seki, Yoshiharu Kawaguchi et al (2013) 219 reported Lumbar Spinal Stenosis

Due to a Large Calcified Mass in the Ligamentum Flavum.

Martel W, McCarter DK, Solsky MA, et al. (1981) 220 reported Chondrocalcinosis and calcium pyrophosphate dihydrate (CPPD) crystals deposition can involve the spine through a variety of mechanisms. Acute and chronic articular chondrocalcinosis may produce destructive lesions of the vertebral body and disc space. This pathology can be confused with infectious discitis and ankylosing spondylitis.

Myelopathy and cervicomedullary compression have been reported on a number of occasions secondary to nodular deposition of CPPD crystals in the ligamentum flavum221, 222or on the atlanto-occipital ligament.223These findings suggest that calcification of the ligamentum flavum may be a rare manifestation of the deposition of

CPPD crystals.

Calcification of the spinal ligaments, mainly the posterior longitudinal ligament and the ligamentum flavum, is a well-known cause of myelopathy and radiculopathy of the cervical and thoracic spine.224, 225, 226

Park JB et al. (2001)9 studied the concentration of transforming growth factor-ß1

(TGF-ß 1) in the ligamentum flavum of lumbar spinal stenosis and disc herniation.

Their results suggested that higher expression of TGF-beta 1 by fibroblasts might be related to the development of hypertrophy of the ligamentum flavum in lumbar spinal

54 Review of Literature stenosis. They alsostudied Hypertrophy of ligamentum flavum in lumbar spinal stenosis associated with increased proteinase inhibitor concentration. It is well known that age-related fibrosis, or decreases in the elastin-to-collagen ratio of the ligamentum flavum, along with hypertrophy of the ligamentum flavum, are associated with lumbar spinal stenosis. However, the molecular mechanism by which this fibrosis and hypertrophy develop is unknown. Tissue inhibitors of matrix metalloproteinase

(TIMPs) are proteinase inhibitors that suppress extracellular matrix degradation. Ele- vated TIMP-1 and TIMP-2 expression has been implicated in various fibrotic diseases of the liver, kidney, lung, and heart. These TIMPs can also induce cellular proliferation and inhibit apoptosis in a wide range of cell types. These findings led us to postu- late that TIMP-1 and TIMP-2 might also be associated with hypertrophy and fibrosis of the ligamentum flavum in lumbar spinal stenosis.

Increased TIMP expression has been implicated in fibrosis and hypertrophy of the extracellular matrix of several organs. Their results suggest that increased expression of

TIMP-2 in ligamentum flavum fibroblasts is associated with fibrosis and hypertrophy of the ligamentum flavum in patients with spinal stenosis.

Hyung-Jun Kim et al. (2007)227studied serum levels of TGF-ß1, TIMP-1 and TIMP-

2 in patients with Lumbar spinal stenosis and disc herniation. They concluded that the local levels of TGF-ß1, TIMP-1 and TIMP-2 were significantly higher in the ligamentum flavum of patients with lumbar spinal stenosis than those with disc herniation.

Furthermore, they found that serum levels of TGF-ß1, TIMP-1 and TIMP-2 were very similar in both groups with no significance difference. These results suggests that the role of TGF-ß1, TIMP-1 and TIMP-2 on hypertrophy of ligamentum in lumbar stenosis patients is not a systemic phenomenon but rather a local one.

55 Review of Literature

Stefan Lakemeier et al. (2011)228 elucidated the role of CD44 and its splice variants

CD44v5 and CD44v6 in the hypertrophied LF obtained from patients with lumbar spinal stenosis (LSS) in their study Increased expression of CD44 in hypertrophied ligamentum flavum and relevance of splice variants CD44v5 and CD44v6.

CD44 and CD44v5 expression were significantly increased in the hypertrophy group

(p < 0.05). CD44v6 expression was not significantly increased. The number of elastic fibers was significantly higher in the hypertrophy group. In the hypertrophy group, LF thickness was significantly increased while CSA was significantly decreased. There was a statistical correlation between LF thickness, CSA, CD44, and CD44v5 expression in the hypertrophy group (p < 0.05). LF hypertrophy is accompanied by increased

CD44 and CD44v5 expression. CD44v6 expression is not enhanced in LF hypertrophy.

Tetsuya Nakatani et. al (2002)229 in their study Mechanical stretching force promotes collagen synthesis by cultured cells from human ligamentum flavum via transforming growth factor-beta1investigated the effect of mechanical stretching force on collagen synthesis and transforming growth factor-beta1 (TGF-ß1) production using ligament cells isolated from human ligamentum flavum in vitro. Ligamentum flavum cells (LFCs) were isolated from human ligamentum flavum obtained from patients who underwent lumbar spine surgery. The LFCs were subjected to a mechanical stretching force using a commercially available stretching device that physically deformed the cells. Collagen synthesis and TGF-ß1 production levels in the LFCs were then examined. Notable increases were observed in the gene expressions of collagen types I, III, and V in LFCs subjected to mechanical stretching force. The increase in collagen gene expression of LFCs was inhibited in the presence of anti-TGF-ß1 anti-

56 Review of Literature bodies. Production of TGF-ß1 by the LFCs also increased significantly by the mechanical stretching force. Exogenous application of TGF-ß1 was confirmed to increase collagen synthesis of the LFCs. This data indicated that mechanical stretching force can promote TGF-ß1 production by LFCs, resulting in hypertrophy of the ligament.

Ossification of the ligamentum flavum(OLF) is a rare entity seen in the United States. It has most commonly been described in the Far East, notably in Japan.230, 231, 232, 233, 234

Sairyo, K; Goel, VK et al. (2005)235found out that a distinctive collagenous layer was clarified to exist in the ligamentum flavum at the dural most aspect, and this relatively stiff layer would prevent the deeper site of the LF against mechanical loading/ stretching, which can cause stress-related injury, during lumbar motion. This could keep the deeper site, where neural tissue is close,intact.

Jianwei Chen et al.(2014)236 found that miR-155 was upregulated in patients with lumbar ligamentum flavum hypertrophy. The expression level of miR-155 was correlated with the thickness and the degree of fibrosis of LF. miR-155 increased the expression of types I and III collagen in fibroblasts from LF. These data suggest that miR-155 is a fibrosis-associated miRNA and may play important role in the pathogenesis of LF hypertrophy.

IMAGING OF SPINAL STENOSIS

Imaging of spinal stenosis began with the plain film radiograph. Myelography then added the dimension of evaluating thecal content contours including the spinal cord, nerve roots, and spinal canal. Computed tomography (CT) allowed for detailed evaluation of the bony spine. Attempts to diagnose spinal stenosis by measuring the dimen-

57 Review of Literature sions of the canal have been disappointing. The combination of myelography and CT further enhanced the ability to assess the spinal canal and its contents by allowing visualisation of the nerve roots, lateral recesses, and spinal cord in multiple planes.

More recently, magnetic resonance (MR) imaging has provided the same imaging ca- pabilities without the need for an invasive procedure (i.emyelography). The spinal fluid provides a myelographic effect on MR imaging. MR imaging is considered the study of choice in the diagnosis of spinal stenosis because disc, soft tissue, bony changes, and intrathecal content are visualized. No imaging technology can diagnose spinal stenosis without a clinical history that is consistent with the diagnosis. Spinal imaging may appear worse than the patient’s symptoms and do not necessarily correlate with clinical findings.237, 238

Plain film radiography

Plain film radiographs provide assessment of the bony structures of the spine.

Neuroforaminal narrowing, facet joint space narrowing, and disc space narrowing are evident using anterior–posterior (AP), lateral, and oblique films in the cervical and lumbar spine (Fig.14). In the cervical spine, an average canal diameter of less than 10 mm indicates stenosis. 239

58 Review of Literature

Fig.15 Lateral lumbar spine film demonstrates Grade 1 to 2 anterolisthesis of L5 in relation to S1. This finding is highly suggestive of canal stenosis. The L5/S1 Neuroforamina are also narrowed from the anterolisthesis and hypertrophic facet changes.

Standing films aid in identifying subluxation and disc space narrowing. Osteophytes associated with disc and joint space narrowing can produce canal and neuroforaminal narrowing, compressing the spinal cord and nerve roots. The ability to determine the degree of canal or neuroforaminal stenosis is poor. Congenitally short pedicles increase the sensitivity of plain film diagnosis of neuroforaminal stenosis.240

Developmental canal stenosis may be present.241Findings on radiographs may not correlate well with clinical symptoms.

Retrolisthesis in the lumbar spine has the best plain film correlation with spinal stenosis. Erosion of the posterior vertebral body or neural foramina indicate a mass effect that may cause stenosis. Lateral flexion and extension radiographs have the best correlation with spinal stenosis. Motion of greater than 2 mm with flexion or extension indicates an unstable spine, resulting in canal or neuroforaminal narrowing.242

Myelography is the introduction of contrast medium into the thecal space through a lumbar puncture needle. The technique is invasive. Contrast is usually injected at the lumbar spine level. In the event of a blockage to the flow of spinal fluid, the contrast may be injected at a high cervical-spine level.

59 Review of Literature

Fig 16. (A) Lateral lumbar spine film demonstrates degenerative disc disease with disc space narrowing, osteophyte formation anteriorly and posteriorly, retrolisthesis of L2 on L3, L3 on L4 and L5 on S1. All these findings contribute to canal or neuroforaminal narrowing, however may not correlate with clinical symptoms. (B) Lateral lumbar spine with kyphoplasty for compression fracture of L3. The posterior cortex of L3 is retropulsed narrowing the spinal canal. Also noted is disc space narrowing/degenerative disc disease and facet degenerative change. (C) Minimal retrolisthesis at L5 on S1, straightening of the lumbar lordosis, disc space narrowing all give the appearance of canal narrowing.

Introduction of contrast results in a silhouetting of the spinal cord and nerve roots to the level of the neural foramen. Assessment within the neural foramen cannot be performed unless CT is used. The outline of the spinal cord with stenosis has a characteristic appearance of an hourglass at one or more

60 Review of Literature levels.243 Disc herniation is frequently unilateral and causes an extradural mass effect.

If the nerve root is cut off or displaced, if the cord is impinged on focally, or if complete blockage exists, the contrast demonstrates the level and shape of the disc, mass, osteophyte, ligamentum flavum hypertrophy, vascular malformation,244 or other causes. Flexion/extension views aid in making the decrease in canal size more obvious.245 The cause of the altered contrast column may not be apparent in many cases.

61 Review of Literature

Is a technique using radiographs acquired by a rotating x-ray tube and multiple detectors. With the use of reconstruction algorithms, an image is generated by a computer

(Fig. 3). Scanners have different numbers of detectors. Sequential imaging was and is used. This is the acquisition of one slice after another in sequence. Spiral scanning is a recent innovation that uses volume imaging that reduces artifact, is rapid (seconds to minutes), and improves resolution by using a significantly larger number of detectors to acquire the image.246

CT has become a revolutionary diagnostic tool (Fig. 4). Diagnosis of spinal stenosis has become a significant problem with CT, however. CT

Fig. 3. Sagittal reformation of the lumbar spine demonstrates vacuum disc with mark- ing narrowing of the disc at L4/L5. Grade 1 anterolisthesis of L4 on L5 is present.

Facet degenerative changes are present and posterior osteophytes at L4. The reformation demonstrates canal and neuroforaminal narrowing at the L4/L5 disc level. without spinal loading (weightbearing) may miss canal stenosis. The use of CT myelography improves the ability to determine compression on the spinal cord, thecal sac, and nerve roots. Neuroforaminal assessment was improved with the use of myelographic contrast.

Bony causes of canal and neuroforaminal stenosis include facet osteophytes, hard discs, compression fractures, and spondylolisthesis. All can be identified and evaluated through high-resolution images and reformations in the sagittal and coronal planes, and multiplanar reconstruction.247 Lateral recess narrowing248 and extrathecal lateral

62 Review of Literature recess narrowing and neuroforaminal narrowing can be detected.249 The transverse diameter of the spinal canal has been evaluated. Measurements of less than

Fig. 17. Axial CT scan demonstrates marked facet degenerative change with severe canal stenosis. Gas is related to vacuum phenomena in a degenerated disc.

10 mm indicate canal stenosis. Measurements between 10 and 12 mm are consistent with relative stenosis. 250 The cross-sectional area of the spinal canal and dural sac have been evaluated using different techniques. Cross-sectional dural sac measurements of less than 75 mm in area are correlated with stenosis. 251 The results may not correlate with clinical symptoms. 252

Soft tissue can be assessed by inference.Contrast in the thecal sac allows the evaluation of contour abnormalities that result in thecal sac, spinal cord, and nerve root compression (Fig. 16).

Fig. 17. (A) Cervical spine axial plane CT-milligram. Note contrast surrounding the spinal cord, nerve roots within the contrast column and contrast in the nerve root sheath in the neuroforamina. (B) Coronal reformation of a cervical spine CT-myelogram. The spinal cord and nerve roots exiting the thecal sac are identified. Contrast is seen in a nerve root sheath in the neuroforamina. Significant facet degenerative

63 Review of Literature changes are present. (C) Sagittal reformation of a CT-myelogram. Spinal cord is seen in the contrast column. Note mild cord compression at C3/ C4 level due to degenerative disc and facet disease.

Fig. 18. Axial image from a CT-myelogram shows mild canal stenosis secondary to a posterior vertebral body osteophyte.

Protruded, extruded, or bulging disc is the source of compression (Fig. 7). Neurologic tumors, drop metastasis, and abscess may also be the source of compression. Posteri- orly, ligamentum flavum redundancy and synovial cysts from degenerated facets may be the source of compression. Approximately 90% of synovial cysts are in the lumbar spine, and 10% are in the cervical spine. 253 The reason for a contour defect may not

64 Review of Literature be determined with complete confidence, only that the defect exists. Based on the position of the compression and other clinical information, the source may be determined.

Fig. 19. CT-myelogram axial image demonstrates mild canal stenosis and marked stenosis of the left neuroforamina from a disc protrusion severely compressing the exiting nerve. Facet degenerative changes are present.

MR imaging

Though similar to CT in that cross-sectional images are produced, the physical princi- ple underlying MR imaging is entirely different. MR analyzes multiple tissue characteristics including hydrogen ion density, T1 and T2 relaxation times of tissue, and blood flow within tissue. Differences in the density of protons available to contribute to the MR signal discriminate one tissue from another. 254

Most tissues can be differentiated by significant differences in their T1 and T2 relaxation times. In simpler terms, MR is based on the ability of a small number of protons within the body to absorb and emit radio waves when the body is placed in a strong magnetic field. When placed in an external magnetic field, a small number of protons are displaced from their alignment by application of the radiofrequency gradient. When the dis-

65 Review of Literature placed protons realign with the main magnetic field, a relatively small pulse of energy is released, detected, localized, and processed by a computer algorithm similar to that used in CT to produce a tomographic image.255 Zander DR, Lander PH. Positionally dependent spinal stenosis: correlation of upright flexion-extension myelography and computed tomographic myelography.

On T1-weighted (T1W) sequences, the cancellous hematopoetic bone is of intermediate signal intensity between fat and muscle. The signal intensity is primarily a reflec- tion of the marrow space with its lipid and hematopoietic elements. The relative signal becomes brighter with increasing age secondary to an increase in the lipid component.

The osseous structures are outlined by thin low-signal intensity from the cortical bone. On T1W images, the central portion of the disc has a slightly decreased signal when compared with the peripheral portion, which in turn blends with an area of even greater decreased signal intensity representing the outer layer of the annulus fibrosis at its confluence with the longitudinal ligament. On T2-weighted (T2W) images, the signal intensities are essentially reversed.256

The epidural space lies between the dura and the bony confines of the spinal canal. Its contents include epidural fat, ligaments, nerves, and blood vessels. The epidural fat has high signal intensity on T1W sequences and lies anterior and anterolateral to the dura, and posterior and posterolateral between the ligamentum flavum. The signal intensity of the cerebrospinal fluid (CSF) is decreased relative to the extradural elements on the T1W images. With T2W images, the signal intensity of the CSF increases, and it acts as an inher- ent myelographic contrast agent. Fat signal is important in the assessment of neuroforaminal stenosis. Decreased or absent fat signal is seen in stenosis.

66 Review of Literature

The spinal cord lies within the subdural space, with its terminal portion at the level of the L1–L2 vertebral body (Fig. 19). The neural elements within the subarachnoid space have an intermediate signal intensity similar tothat of intervertebral disc on

T1W sequences but is of decreased signal intensity relative to CSF and disc on T2W sequences. The cauda equina is the downward passing of the lumbar and sacral nerve roots at the level of the conus. At the L1–L2 level, they are seen as a mass of soft tissue signal in the dependent portion of the thecal sac. At the L3 level, their most common appearance is as a group of fibers that are present posteriorly in a smooth cres- centic or globular shape. The roots about to exit the dura are located anterior or an- terolaterally in a symmetric pattern. At the L4 level, they are dispersed enough to be seen as separate delicate entities arranged symmetrically within the CSF.

Fig. 20 Sagittal T2 weighted MR image of the lumbar spine. The conus medullaris terminates at the L1 level. Filum-terminale is seen to the level of L2. Slight decrease in signal at the L5/S1 disc is secondary to desiccation/degeneration.

At the L5 level, the few roots present are equally spaced in the thecal sac. Midline sagittal imaging shows the roots as a single linear area of intermediate-signal intensity following the posterior thecal sac. The roots gradually taper from the conus to the L4

67 Review of Literature level where the parasagittal images show them to be fanning out in a posterior superi- or to anterior inferior direction (Fig. 20).

The transverse portion of the nerve root passes downward from the conus within the dural sac and extends anteriorly and laterally at the level of the disc space. The transverse portion of the levels below lie in the lateral recess formed when the superior articular facet becomes contiguous with the pedicle below. The nerve root sleeves usually end ventrally near the medial border of the superior articular facets at the inferior portion of the neural foramina of the level above. The traversing nerve becomes the exiting nerve when it passes laterally underneath the pedicle and into the foramen. On both axial and parasagittal T1W images the nerve roots appear as areas of decreased signal intensity surrounded by epidural fat (Fig. 20).

Spinal stenosis

Spinal stenosis results from an overall decrease in the dimensions of the spinal canal, lateral recesses, or neural foramina. It occurs more commonly in the lumbar and cervical region. Etiologically, stenosis can be divided into two main categories. 257 The first is developmental or congenital, which is idiopathic and includes entities such as achondroplasia, Morquio disease, fluorosis, postoperative changes, and various bony dysplasias.258

Stenosis may be associated with thick short pedicles and a reduced interpedicular

68 Review of Literature

Fig. 21. Normal T1 weighted parasagittal image shows nerve root traversing the neuroforamina along with associated vascular structures. distance and is often worsened by the second type: acquired stenosis that may be a result of degenerative disease, trauma, spondylolisthesis, or postoperative and various miscellaneous conditions such as ankylosing spondylosis, ossification of the posterior longitudinal ligament, degenerative disease, acromegaly, Paget’s disease, and fibrosis. Regardless of the cause, the common denominator of spinal stenosis is narrowing of the canal, which may be central, lateral, or both.

In the lumbar spine, central stenosis tends to occur at multiple levels but is most common at L4–L5, where the canal has a trefoil appearance. The central canal is sus- ceptible to impingement by osteophytes from the vertebral bodies or the facet joints, thickening of the posterior longitudinal ligament, and bulging of the disc. Central canal stenosis is seen at multiple levels but with degenerative diseases is most severe at L4–L5. Upright MR, a recent advance, loads the spine, allows for flexion and extension, and makes stenosis more obvious (Fig. 21 A,B) 259

69 Review of Literature

The transverse and sagittal dimensions of the central canal are best depicted by the orthogonal planes on T2W sequences, providing the best views of the thecal sac dimensions.

Lateral stenosis may occur alone or in combination with central stenosis (Fig. 22).

The height of the lateral recess is defined as the distance between the most anterior portion of the superior articular facet and the posterior aspect of the vertebral body in the same plane. A decreased height is associated with symptoms. Further laterally, neural foraminal stenosis can result from bony overgrowth, spondylolisthesis, or degenerative disc bulge or herniation of the intervertebral disc. It must be remembered, however, that severe morphologic changes can be present without symptomology. Pe- ripheral stenosis is best appreciated on T1W images, which demonstrate the difference between neural elements and fat quite well.

Fig. 22. (A) T2 weighted sagittal image of the lumbar spine. Disc bulge at L4 with facet degenerative changes result in canal stenosis. Linear signal that appears to be nerve roots is prominent vascularity. Note disc desiccation at L3/L4 to L5/S1. (B) Axial T1 weighted image shows ligamentum flavum redundancy, facet degenerative changes resulting in canal and neuroforaminal stenosis.

70 Review of Literature

In the lumbar region, the parasagittal and axial images together allow identification of the lateral recesses and the neural foramina. Malalignment present in spondylolisthesis produces anatomic derangements of the neural foramina that cause stenosis. Asso- ciated true disc herniation is uncommon at the level of the spondylolisthesis but may be found at the levels above.259

71 Aim and Objectives

AIM AND OBJECTIVES

AIM:

To evaluate morphological and histological changes in ligamentum flavum in degenerative lumbar canal stenosis.

OBJECTIVES:

1. Morphological changes occurring in ligamentum flavum in degenerative spine.

2. Histological changes occurring in ligamentum flavum in degenerative spine

3. Relationship between inflammation and scar formation in the ligamentum

flavum.

72 Materials and Method

MATERIALS AND METHOD:

Study Design:

This prospective multidisciplinary study involving clinical, radiologic and histologic assessment using human samples of the lumbar ligamentum flavum was carried out in the department of Orthopaedics and department of Pathology, Jawaharlal Nehru Med- ical College & Acharya Vinoba Bhave Rural Hospital, Wardha from October 2012 to

April 2015.

Total 47 patients were included in the study of those who came to our hospital after fulfilling the inclusion criteria. Out of these 35 patients (20 males and 15 females) were diagnosed as Lumbar spinal Stenosis and 12 (8 males and 4 females) were diagnosed as having Lumbar Disc herniation. All patients were explained about the study and written consent was taken.

Inclusion Criteria:

1) All cases who were admitted in our hospital.

2) All cases taken for spine surgery and who needs ligamentum flavum removal.

3) Cases of all age groups were studied with special emphasis on degenerative spine.

Exclusion Criteria:

1. All patients who were not willing to sign written consent.

2. All cases with spinal deformity such as scoliosis or kyphosis, fracture spine, tu-

mours or infection of spine were excluded from the study.

Protocol And Technique :

The institutional ethics committee approved this study.

73 Materials and Method

All patients who presented to our hospital from October 2012 to April 2015 were included in the study.

Forty seven (47) patients were included in this study (28 men and 19 women)

(Table. 3).

35 of 47 patients belonged to the Lumbar spinal canal stenosis group (males - 20, females

- 15), mean age - 50.51 years, (minimum- 41 years, maximum - 72 years) and remaining

12 patients belonged to lumbar disc herniation group (males - 8, females - 4), mean age -

34.33 years , (minimum - 28 years, maximum - 40 years) (Table.2).

Patients with spinal deformity such as scoliosis or kyphosis, fracture spine or infection of spine were excluded from this study.

The study protocol was approved by institutional ethics committee and consent form was signed by each subject.

Table.3

TOTAL PATIENTS 47 MALES 28 FEMALES 19

GENDER DISTRIBUTION

40% FEMALE MALE 60%

TOTAL PATIENTS-47 FEMALE-19 MALE-28 74 Materials and Method

Fig.23

Table.4

spinal stenosis group no. of patients

males 20 females 15 TOTAL 35 disc herniation group no. of patients

males 8 females 4 TOTAL 12

SPINAL STENOSIS GROUP

43% FEMALE MALES 57%

TOTAL PATIENTS: 35 FEMALES: 15

Fig. 24

75 Materials and Method

DISC HERNIATION GROUP

33%

FEMALES MALES 67%

TOTAL PATIENTS: 12 FEMALES: 4 MALES: 8

Fig. 25

In standardised format, data concerning patients’ history and clinical symptoms were collected.

35 patients belonged to Lumbar spinal stenosis group and 12 patients belonged lumbar disc herniation group.

The main clinical complaint was low back pain in 42 of 47 patients 5 patients were without low back pain. 40 of 47 patients showed additional radicular symptoms. In all, 35 patients complained of neurogenic claudication (30 in combination with low back pain, 5 without low back pain) with an average pain free walking distance of 100 metres. All patients underwent MR Scan to confirm lumbar spinal stenosis and or lumbar disc herniations that was consistent with pain pattern and level of neurologic deficit. All patients were clinically examined completely including the neurological examination (Table 3 - spinal stenosis group), (Table 4 - disc herniation group).

76 Materials and Method

Table 5.Clinical signs and symptoms and neurological defects in patients with spinal stenosis (n = 35)

Neurogenic claudication

with low back pain 30 without low back pain 5 Low back pain with radicular symptoms 25 without radicular symptoms 5 Neurologic Defects Motor EHL weakness - 10 Ankle weakness - 1

Sensory 9 Reflexes 5 Lasegue’s 5

Table 6 Clinical signs and symptoms and neurological defects in patients with Disc herniations (n = 12)

Radicular pain with low back pain 9 without low back pain 3 Neurologic defects Motor 4 Sensory 5 Reflexes 1 Lasegue’s 9

77 Materials and Method

Measurements of the Ligamentum Flavum:

All patients who were clinically diagnosed of having spinal canal stenosis in the lumbar region were sent for MRI scan. Measurements of ligamentum flavum were taken as follows.

We used PACS software and a PACS workstation (GE Medical Systems, 1.5 Tesla super conduct magnet) to measure the thickness of ligamentum flavum. The measurements were taken independently by two different persons including one radiolo- gist.

An axial T1- weighted MR images were obtained at the facet joint level for each patient.The thickness of Ligamentum Flavum was measured at the respective level for each patient at the facet joint level.

On the T 1 – weighted axial images through the facet joint, the ligamentum flavum is seen as a low signal intensity mass just ventral side of facet joint.

Total 180 ligamentum flavum were measured in 47 patients.

The right and left ligamentum flavum (LF) for the involved vertebral level were measured. Thickness at the middle portion of ligamentum flavum was measured. All measurements were taken by 2 persons separately and mean was calculated.

78 Materials and Method

Fig.26 Measurement of ligamentum flavum thickness was carried out at the intervertebral disc level, perpendicular to the lamina border.

Fig. 27. Shows MR picture with Fig. 28 shows how measurement was taken on irregular Hypertrophied ligmentumn flavum. Hypertrophied ligamentum flavum.

All patients underwent decompressive surgery of the spinal canal because of signs and symptoms of degenerative lumbar spinal stenosis.The indication for the surgery were based on clinical, neurophysiological and radiological findings of spinal stenosis.

Posterior decompression of the lumbar spine was performed with removal of the ligamentum flavum.

A total of 87 ligamentum flavum were harvested 79 from the canal stenosis group and

8 from disc herniation group, using a standardised technique. Ligamentum flavum tissue was harvested at L3 - L4 in 13 patients, L4 - L5 in 33 patients and at L5 - S1 in

33 patients (Table. 5) from total 35 patients (men - 20, women -15) (mean age - 50.51 years).

79 Materials and Method

Table. 7

CANAL STENOSIS GROUP

S NO. LEVEL NO. OF LIG. FLAVUM HARVESTED

1 L3 - L4 13 2 L4 - L5 33 3 L5 - S1 33 TOTAL 79

DISC HERNIATION GROUP

Samples of ligamentum flavum tissues of 12 patients (8 men, 4 women; mean age

34.33 years, range 20 - 40 years) who underwent decompression surgery for lumbar disc herniation were used for comparison.

Table. 8

S NO. LEVEL NO. OF LIG FLAVUM HARVESTED

1 L4 - L5 8 2 L5 - S1 7 TOTAL 15

Histopathological analyses:

The harvested ligamentum flavum samples were fixed with 10% buffered formalin for

48 hours and were further embedded into a paraffin block.

Serial 4 µm thick sections were examined after being deparaffinized with xylene and replaced by ethanol, followed by staining with haematoxylin and eosin stain,

80 Materials and Method

Trichrome stain and Verhoeff stain using standard methods. All sections were examined under a light microscope.

1) Trichrome Stain: The degree of fibrosis was evaluated and graded with reference

to its severity (range 0-4).

Grade 0 – indicates normal tissue showing no fibrotic region

Grade 1 – fibrosis at ≤ 25 %

Grade 2 – between 25 % and 50 %

Grade 3 – between 50 % - 75 %

Grade 4 - ≥ 75 %.

(2) Verhoeff Stain:The elastic fibers were stained. The loss elastic fibers were also graded using the same scoring system as the fibrosis score.

Grade 0 – black colour stained all area of the ligamentum flavum, indicating rich elastic fibre content

Grade 1 – loss of elastic fiber ≤ 25 %

Grade 2 – loss of elastic fibre between 25 % and 50 %

Grade 3 – between 50 % - 75 %

Grade 4 - ≥ 75 %.

81 Materials and Method

FIG. 29 grading by histologic changes by trichrome (A) and Verhoeff-van Gieson (B) staining. Figure 1 A demonstrates ligamentum flavum with grades 0 and 4 fibrosis. In grade 0 all area of the ligamentum flavum was stained a pink colour, and a blue colour stained the minimum area, indicating fibrosis. On the other hand, in grade 4, blue stained most of the areas, indicating that most of the area was fibrosis. The loss of elastic fibres was graded using the same scoring system as the fibrosis score (loss of elastic score) by Verhoeff staining. Figure 1 B demonstrates grades 0 and 4 of the loss of elastic fiber scores. In grade 0, a black colour stained all area of the ligamentum flavum, indicating that the area has a rich elastic fiber content. On the other hand, in grade 4, the black-stained area was minimal, indicating loss of elastic fibers.

3) Haematoxyllin & Eosin stain (Calcification):

In H & E stain calcification stains bluish in colour with pink eosinophilic background.

In slides with extensive calcifications the areas stained bluish in colour at many sites.

Two persons (R.A., an orthopaedic surgeon, and S.S., a pathologist) simply estimated these gradings. The relationships of these fibrotic, loss of elastic fiber scores and calcification with thickness of ligamentum flavum measured by T1 – weighted axial magnetic resonance imaging (MRI) examination before the surgery were evaluated at each site of the ligament.

82 Materials and Method

83 Observation and Results

OBSERVATION AND RESULTS:

Gross:

The surface of ligamentum flavum on the ventral side is not uniform and smooth always it ranges from smooth to eroded, creases in the ligamentum flavum as results of folding of the ligament. The dorsal side was never smooth it was in all cases irregular, thick, rough and hypertrophied.

CLINICAL STUDY:

Fig 30 measurements taken on MRI Scan using PACS software.

Ligamentum flavum thickness was measured in total 180 ligaments on T1 weighted axial images on plain MR Scan.

84 Observation and Results

Overall the thickness increased with age at all levels however the increase was most pronounced at L4/L5.

85 Observation and Results

Table No. 9 SPINAL STENOSIS GROUP:

SPINAL LEVEL NO. OF LIGAMENTUM MEAN THICKNESS FLAVUM (mm)

L1/L2 2 3.1875 L2/L3 5 3.63 L3/L4 14 3.680 L4/5 33 4.535 L5/S1 33 3.8

Mean thickness of Ligamentum Flavum at differrent Levels 4.6

3.45

2.3 Thickness

1.15

0 L1 - L2 L2 - L3 L3 - L4 L4 - L5 L5 - S1

LEVEL

FIG. 31 change in thickness with aging at each spinal vertebral level.

The thickness of ligamentum flavum at L4/L5 levels continuously increased with age.

The mean thickness of the ligamentum flavum in all patients was 3.1875 mm, 3.63 mm,

3.680 mm, 4.535 mm and 3.8 mm for L1/L2, L2/L3, L3/L4, L4/L5 and L5S1 levels, respectively. The thickness of the ligamentum flavum was highest at L4/L5 level.

86 Observation and Results

4.5

L4-L5 3 L3-L4 L5-S1 Thickness

1.5

0 40-50 50-60 60-70 70-80 Age Group (Years)

Fig. 32 Mean thickness of ligamentum flavum in different age groups at L3-L4,

L4-L5, L5-S1 level.

87 Observation and Results

Table No.10 LIGAMENT THICKNESS AT L3 - L4 LEVEL

AGE (years) NO. OF PA- MEAN MINIMUM MAXIMUM TIENTS THHICK- THICKNESS THICKNESS NESS (mm) (mm) (mm) 40 - 50 5 3.81 3.125 4.775 50 - 60 4 3.706 3.375 4.225 60 - 70 4 3.312 2.925 3.6 70 - 80 1 4.1 — —-

Table No. 11 LIGAMENT THICKNESS AT L4 - L5 LEVEL

AGE (years) NO. OF PA- MEAN MINIMUM MAXIMUM TIENTS THICKNESS THICKNESS THICKNESS (mm) (mm) (mm) 40 - 50 19 4.510 3.2 5.25 50 - 60 10 4.7525 4.0 5.5 60 - 70 5 4.838 4.45 5.0 70 - 80 1 5.1 —— 5.1

Thickness of Ligamentum flavum (L4 - L5) 5.1

4.9

4.7

Thickness (mm) 4.5

4.3 40 - 50 50 - 60 60 -70 70 - 80 Age (years)

88 Observation and Results

Fig. 33 Mean thickness of ligamentum flavum at L4-L5 in Different age groups

Table No.12 LIGAMENT THICKNESS AT L5 - S1 LEVEL

AGE NO. OF MEAN MINIMUM MAXIMUM (years) PATIENTS THICKNESS THICKNESS THICKNESS (mm) (mm) ( mm)

40 - 50 17 3.930 2.355 5.075 50 - 60 9 4.055 2.825 4.675 60 -70 5 3.61 3.025 4.4 70 - 80 1 4.425

L3-L4

70-80 L4-L5 60-70 Level 50-60 40-50 L5-S1

0 1.5 3 4.5 6

Thickness (mm)

Fig.34 shows thickening of ligamentum flavum at L3 -L4, L4 - L5 and L5 - S1 levels at different age groups.

The ligamentum flavum at L5 - S1 level increased with age except in the age group

60 - 70, less number of subjects may be a reason. However ligament thickness at L3 -

L4 level do not show an increase trend with the age, may be a larger number of subjects at this level can give more accurate result.

However an increase trend was found between increasing age groups and thickness of ligamentum flavum at L4 -L5 level as the thickness of ligamentum flavum at L4 - L5

89 Observation and Results level continuously increased with age though the correlation was not statistically significant.

Table No. 13 THICKNESS OF LIGAMENTUM FLAVUM IN DISC HERNIA-

TION GROUP:

LEVEL MEAN THICKNESS OF LIG. FLAVUM (mm)

L4 - L5 3.142 L5 - S1 3.268

Thickness of Ligamentum flavum in Disc herniation group 3.3

3.225

3.15

Thickness (mm) 3.075

3 L4 - L5 L5 - S1

Level

FIG. 35 Mean thickness of ligamentum flavum at L4 – L5 and L5 – S1 level in

Disc herniation group.

Thickness of ligamentum flavum in the disc herniation group was 3.142 mm at L4 -

L5 level and 3.268 mm at L5 - S1.

Hence thickness of ligamentum flavum was comparatively less in the disc herniation group at the L4 - L5 level compared to the spinal stenosis group.

90 Observation and Results

HISTOLOGICAL EVALUATION OF THE LIGAMENT:

NO. OF LIG. FLAVUM HARVESTED

Table. No. 14 CANAL STENOSIS GROUP

S NO. LEVEL NO. OF LIG. FLAVUM HARVESTED

1 L3 - L4 13 2 L4 - L5 33 3 L5 - S1 33 TOTAL 79

Table No. 15 DISC HERNIATION GROUP

S NO. LEVEL NO. OF LIG FLAVUM HARVESTED

1 L4 - L5 4 2 L5 - S1 4 TOTAL 8

A total of 87 ligamentum flavum were harvested 79 from the canal stenosis group and

8 from disc herniation group, using a standardised technique. Ligamentum flavum tissue was harvested at L3 - L4 in 13 patients, L4 - L5 in 33 patients and at L5 - S1 in

33 patients from total 35 patients (men - 20, women -15) (mean age - 50.51 years)

(Table. 5).

91 Observation and Results

A total of 8 Samples of ligamentum flavum tissues of 12 patients (8 men, 4 women; mean age 34.33 years, range 20 - 40 years) who underwent decompression surgery for lumbar disc herniation were used for comparison.

Table No. 16 Trichrome stain (fibrosis score):

FIBROSIS MEAN MINIMUM MAXIMUM SCORE THICKNESS THICKNESS THICKNESS (GRADE I - IV) (mm) (mm) (mm)

GRADE - I 4.35 3.2 4.95 GRADE - II 4.50 4.0 4.875 GRADE - III 4.569 4.025 5.25 GRADE - IV 5.01 4.25 5.75

The Mean thickening of the ligamentum flavum increased with increasing grade of the fibrosis, showing a strong linear correlation which is also statistically significant

(p value < 0.05).

Fibrosis Score 5.1

4.9

4.7

Thickness (mm) 4.5

4.3 Grade I Grade II Grade III Grade IV

Fibrosis SCore

92 Observation and Results

Fig. 36 Shows the correlation between the fibrotic score for the entire ligamentum flavum and thick-

ness of the ligamentum flavum.

The relationship between ligamentum flavum thickness and fibrosis score showed positive linear, strong correlations. (P value < 0.05).

GRADE - I GRADE - IV

Fig. 37 In grade I all area of the ligamentum flavum was stained a eosinophilic pink colour, and a blue colour stained the minimum area, indicating fibrosis. On the other hand, in grade IV, blue stained most of the areas, indicating that most of the area showed fibrosis.

93 Observation and Results

Table No. 17 VERHOEFF STAIN (LOSS OF ELASTIC FIBRE):

LOSS OF ELAS- MEAN THICK- MINIMUM MAXIMUM TIC FIBER NESS THICKNESS THICKNESS SCORE (mm) (mm) (mm) GRADE - 0 4.13 3.2 4.95 GRADE - I 4.41 3.825 5.25 GRADE - II 4.70 4.325 5.0 GRADE - III 4.870 4.65 5.25 GRADE - IV 5.15 4.85 5.65

LOSS OF ELASTIC FIBRE SCORE COMPARED WITH MEAN THICKNESS OF LIGAMENTUM FLAVUM

An increase trend was found when Loss of elastic fibre score were compared with the mean thickness of the ligamentum flavum. The thickness of ligamentum flavum increased with the increasing grade of loss of elastic fibre group. The relationship be-

94 Observation and Results tween ligamentum flavum thickness and loss of elastic fibre score showed positive linear, relatively strong correlations. (P value < 0.05.)

! !

GRADE I GRADE IV

Fig. 38 represents the histology of the severely hypertrophied ligament, less elastic fibres were stained with Verhoeff stain6 in grade IV, On the other hand the elastic fibres were well stained in grade I.

4.5

Thickness (mm) 1.5

0 GRADE 0 GRADE I GRADE II GRADE III GRADE IV Grade

95 Observation and Results

Fig.39 Mean thickness of ligamentum flavum in different grades of loss of elstic

fibre score

CALCIFICATION:

In patients with lumbar spinal stenosis, 83 of 87 ligaments were calcified.

All patients in whom calcification was found in the ligamentum flavum were divided in three groups.

Patients were classified into three age groups as follows:

I - those aged 40 - 50 years (19 biopsies)

II - those aged 50–60 years (26 biopsies)

III - those aged above 60 years (18 biopsies).

Table. 18 CALCIFICATION IN DIFFERENT AGE GROUPS

AGE GROUP NO. OF PTS NO. OF LIG CALCIFICA- FLAVUM TION

I (above 60 years) 6 18 18 II (50 - 60 years) 10 26 24 III (40 - 50 years) 19 43 41 TOTAL 35 87 83

The percentage of calcification increased with age across the three groups (I> II > III)

(Table 3). An increase trend could be seen in the calcification as the percentage of calcification increases with the increasing age. However it is statistically not significant.

Table No. 19 Calcification in Disc Herniation Patients in Different Age Groups

96 Observation and Results

AGE NO. OF NO. OF LIGAMENTUM CALCIFICATION GROUP PATIENTS FLAVUM 20 - 30 2 2 NO CALCIFICATION 30 - 40 10 12 4

In the disc herniation group which 4 of 12 ligaments showed minimal calcification.

The ligaments were divided into age groups as 20-30 and 30-40 years. Only in age group 30 - 40 years were calcified ligaments found. Compared to the disc herniation the average percentage calcification of the ligamentum flavum in lumbar spinal stenosis was significantly higher.

Minimal Calcification (slide a) Extensive Calcification (slide b)

Fig. 40 histopathological sections in slide ‘a’ showing H & E stain with minimal calcification stained

bluish in colour (arrow), with pink eosinophilic background. Where as in slide ‘b’ the areas stained

bluish in colour have increased and can be seen at many sites (arrows) suggesting extensive

calcification.

97 Observation and Results

In the Disc herniation group, only 4 of 20 ligaments showed minimal calcification.

The ligaments were divided into the same three age groups as above. Only in age group I were calcified ligaments found.

A relationship between age and degree of calcification could only be seen as a trend

(the older the more calcified), but was statistically not significant (P > 0.05).

98 Observation and Results

Table No.20

CALCIFICATION MEAN MINIMUM MAXIMUM THICKNESS THICKNESS THICKNESS (mm) (mm) (mm)

NO CALCIFICATON 4.005 3.0 4.75 MINIMAL 4.545 4.0 4.95

MODERATE 4.606 4.125 5.3

EXTENSIVE 5.103 4.325 5.875

Calcification compared with Ligamentum flavum thickness 6

4.5

Thickness (mm) 1.5

0 No calcification Minimal Moderate Extensive

Fig . 41 calcification compared with meanCalcification thickness of ligamentum flavum

In the disc herniation group which was considered as a control group, only 4 of 20 ligaments showed minimal calcification. The ligaments were divided into the same three age groups as above. Only in age group I were calcified ligaments found. A relationship between age and degree of calcification could only be seen as a trend (the older the more calcified), but was statistically not significant.

The average percentage calcification of the ligamentum flavum in lumbar spinal stenosis was significantly higher compared to the disc herniation group.

99 Observation and Results

100 Observation and Results

101 Discussion

DISCUSSION:

The ligamentum flavum covers the posterior wall of the spinal canal. Thus as the ligamentum flavum hypertrophies, it will compress the spinal cord, cauda equina, or nerve root. Hypertrophy of ligamentum flavum is one of the major factors of canal narrowing in lumbar spinal canal stenosis.

In 1913, Elsberg8 first reported the case showing sciatica caused by the ligamentum flavum hypertrophy. Many clinical reports followed to indicate that ligamentum flavum hypertrophy was main pathology inducing significant clinical symptoms in patients with lumbar spinal canal stenosis.1, 3-5 9, 13

Numerous studies have investigated the mechanism of ligamentum flavum hypertrophy from the view points of anatomy, histology, and biology.3, 8-15

To date, few viable hypotheses have been established regarding the pathomechanism of ligamentum flavum hypertrophy.

In our present study we have carried out clinical, radiological and histological study on ligamentum flavum.

The causes of ligamentum flavum hypertrophy are multifactorial including activity levels, age, and mechanical stress. To elaborate these causes in details, several attempts have made in literature to clarify the pathomechanism of the ligamentum flavum hypertrophy.

The only therapeutic manoeuvre for patients with symptoms caused by ligamentum flavum hypertrophy is surgical removal of the hypertrophied ligament. If the pathomechanism is clarified, nonsurgical treatment options could be pursued. Thus an understanding of the pathomechanism of the ligamentum flavum hypertrophy would be very valuable.

102 Discussion

Clinical study:

GROSS: The surface of ligamentum flavum on the ventral side is not uniform and smooth always it ranges from smooth to eroded, creases in the ligamentum flavum as results of folding of the ligament. The dorsal side was never smooth it was in all cases irregular, thick, rough and hypertrophied. These findings are consistent with Teruaki

Okuda et al.12

A possibility was reported that disc collapse associated with disc degeneration led to a decrease in intervertebral height and frequently buckled the thickened ligamentum flavum.21, 210

In the present study we measured the thickness of 180 ligamenta flava from 47 subjects in the age groups ranging from 40 to 80 years age (Mean age - 50.51 years) in

Lumbar spinal stenosis group whereas it was 20 to 40 years (mean age - 34.33 years) in Lumbar disc herniation group.

The thickness of ligamentum flavum was found to increase with age. A trend can be seen that the thickness of ligamentum flavum increases with age however statistically it was not significant. However, the changes with age showed spinal level dependence. The increase in thickness with age was largest at L4/L5, probably because of increased mechanical stress at this level. These findings are consistent with the results of Koichi Sairyo et. al (2005).217

The shape of the lumbar spinal canal varies and may be an oval, rounded triangular or trefoil configuration.46 The trefoil configuration usually occurs at the fifth lumbar level, making L4-L5 the narrowest level.47And occurs in 25 % population, only appear-

103 Discussion ing in adulthood.48 The anteroposterior diameter of the lumbar spinal canal is critical in the pathogenesis and is affected by the length of the pedicles.21

Although factors like body weight, activities of daily living, including occupation exposure and recreational activity, could affect the ligamentum flavum thickness but not considered in the present study. The purpose of the clinical portion of the present study was to understand the natural course of the variations in thickness of the ligamentum flavum.

Koichi Sairyo, Vijay Goel et. al217 discovered the loading mode that will relatively induce the most tensile stress. They observed that maximum stress was observed in flexion mode. Thus, a mode that requires flexion such as lifting may lead to ligament hypertrophy.

In 1938 Naffziger et. al47 was the first to state that hypertrophy of the ligamentum flavum was the result of injury with scar formation.

Similarly in 2005 Koichi Sairyo, Vijay Goel et. al217 reported that the dorsal side of ligamentum is highly stressed during the activities of daily living. During lumbar motion, mechanical stress causes damage in the ligament and the repairing process in the ligament fibrosis occurs similar to scar formation.

HISTOLOGIC STUDY:

In our study we also focussed on major histological changes. Total 87 ligamenta flava were harvested during surgery and subjected to the histological study.

79 ligamenta flava from the spinal canal stenosis group and 8 ligamenta flava from the disc herniation group.

104 Discussion

The following stains were used 1) Haematoxillin and Eosin stain 2) Masons

Trichrome stain 3) Verhoeff stain.

87 ligaments were stained with H & E staining and Trichrome stain whereas 30 ligaments were stained with Verhoeff stain.

Fibrosis (Trichrome stain):

The fibrosis score showed a positive linear correlation with ligamentum flavum thickness, and statistically it was significant (p value < 0.05). In our histological study using Masons trichrome staining the fibrosis appeared in all areas of a hypertrophied ligamentum flavum. Fibrosis is a type of scarring that occurs as a result of injury. Scar formation has been reported in the repair process following injuries in ligaments such as medial collateral ligament of the knee joint therefore hypertrophied ligamentum flavum could have suffered a stress related injury leading to scar formation.

These findings are consistent with the results of Koichi Siaryo et. al216 They reported in their study that accumulation of scar tissue could be an important factor in the development of ligamentum flavum hypertrophy. Dorsal layer showed the most pronounced fibrotic damage.

Elastic fibers (Verhoeff stain):

It has been reported that in young ligamentum flavum, the elastic fibre content is high and it decreases with aging.122, 85, 21, 217

This collagen/elastin conversion is considered to be one of the pathomechanism of ligamentum flavum hypertrophy. In our study the histologic results with Verhoeff staining showed that the loss of elastic fibers correlated with ligamentum flavum hy-

105 Discussion pertrophy. Thus it supports the theory that increased collagen (fibrosis) could be the main factor in collagen/elastin conversion without decreasing the elastic fiber content.

It was noted in our study even in Grade I the elastic fibres were not parallel as it is noted in non-degenerative ligamenta flava i.e the fibres should appear parallel.This was consistent with Menson and Fender.46

According to Menson and Fender46 the angles of the elastic fibres in non-degenerative ligamenta flava should remain approximately equal, i.e. the fibres should appear par- allel46 A strict parallel order of the elastic fibres in the ligamentum flavum shown by

Menson and Fender is characteristic of healthy specimen.46

Our study also showed that this parallel order could no longer be found in the ligamenta flava in lumbar spinal stenosis. These findings are consistent with the results of

Yoshida et al.86

Also Peter K. Schräderet.al260 measured every fibre angle in the ligament; they proved that the parallel order of the elastic fibres of the ligamentum flavum is lost in degenerative lumbar spinal stenosis.

Calcification:

Studies on ossification of spinal ligaments due to systemic diseases are mostly found in the Japanese literature. It is reported to occur predominantly in the thoracic and cervical spine, causing spinal stenosis, eventually associated with neurologic symptoms.230, 231, 232, 233, 234

Ossification of the ligamentum flavum in these cases is based on hypertrophy of the ligamentum flavum with cartilaginous tissue proliferation.261

106 Discussion

Calcification of the ligamentum flavum is reported to appear more often in combination with other degenerative changes of the spine. Avrahami et al.195 indicates an incidence of

80% in a group of 30 patients with radiologically confirmed lumbar spinal stenosis.

Calcification of ligamentum flavum is a rare entity, reported more commonly in patients from Japan and the French Antilles. It is usually seen in middle-aged woman and most commonly affects the cervical spine. It is thought to be due to deposition of calcium pyrophosphate within the ligamentum flavum. The calcification may be symptomatic if it abuts the spinal cord, and surgery is usually helpful for symptomatic patients.230, 231, 232, 233, 234 Although this fact is considered a manifestation of degenerative disease of the spine, it barely has been studied, and many questions remain unresolved.

Calcification is common in Asian population in lower thoracic and cervical spine and rare in western population.230, 231

Baba et al.8 reported in five patients who underwent lumbar decompressive surgery for cauda equina syndrome and radiculopathy secondary to degenerative stenosis associated with calcium deposition in the ligamentum flavum. Histology showed marked degeneration in elastic fibres and diffuse to massive calcium deposition in the ligamentum flavum. This was interpreted as being associated with the degenerative process in the ligament, and changes were suspected as causing or aggravating the neurological symptoms. A quantitative analysis of calcification was not performed.

No information is given to describe the degree of degeneration of elastic fibres.

Yoshida et al.9 studied 45 cases of lumbar spinal stenosis by CT and pathologic and immuno-histochemical studies. As controls, ten cases of acute disc herniation were used. Statistically significant differences in thickness and transverse area were found compared to the controls. The pathogeneses of the hypertrophied ligamenta flava were

107 Discussion classified into three major groups: (1) fibrocartilage change due to proliferation of type II collagen, (2) ossification, and (3) calcium crystal deposition.

Postacchini et al.21 examined ligamenta flava obtained from nine patients with lumbar disc herniation and ten patients with lumbar spinal stenosis. The ligaments were studied at histological, histochemical, and ultrastructural levels. Controls comprised ligaments from six patients undergoing surgery for thoracolumbar fractures. In lumbar spinal stenosis, degenerating elastic fibres were seen occasionally, while calcification could be seen often. Histological findings concerning degeneration were observed in controls aged 50 or older; similar histological features could be found in patients with disc herniation of similar ages.

Schrader et al.260 evaluated twenty-one patients (13 men, 8 women, age range 44 -

80) who underwent decompressive surgery of spinal canal because of signs and symptoms of degenerative lumbar spinal stenosis. In patients with lumbar spinal stenosis,

35 of 38 ligaments were calcified. As the distribution of age was heterogenous, the degree of calcification in relation to the age was set. The percentage of calcification increased with age across the three groups. In control group, 3 of 20 ligaments showed minimal calcification.

In our study 80 of 87 ligaments were calcified ranging from extensive calcification to minimal calcification. Calcification of the ligamentum flavum as described in our study represents a process of physiologic aging.

108 Discussion

Due to close proximity of ligamentum flavum to dura and spinal nerves, it is obvious that ligamentum flavum may contribute considerably to the pathogenesis of lumbar spinal stenosis.

Our analysis of calcification of the ligamentum flavum proves that this degenerative process can cause sciatic or neurological clinical findings in lumbar spinal stenosis.These findings are consistent with the results of Schrader et al.260

Postacchini et al21 found age related changes in the ligamentum flavum too. These findings are consistent with our results.

Thus it can be assumed that apart from reduced elasticity of the ligamentum flavum a concomitant increase of volume of the ligament due to ‘calcification’and reduction of elastic fibres may contribute to the pathogenesis of lumbar spinal canal stenosis.

Many authors 4, 8, 13, 14, 11, 15, 16, 17, 10 in the past have described an association between changes of the ligamentum flavum and degenerative lumbar spinal stenosis.

In this study, we have described the role of calcification in ligamentum flavum hypertrophy, these findings are consistent with the results of Schrader et al.260

Kazuo Miyasaka, Kiyoshi Kaneda, et al.262 reported that ossification and calcification of the ligamentum flavum have different clinical, radiologic, and histologic presenta- tions.

Although ossification of the ligamentum flavum has become an important disease (as a cause of thoracic radiculomyelopathy), patients with the condition are sometimes still not correctly diagnosed for months and years.

This is probably due to two reasons. First, bony spicules or ossification at the capsular insertion of the ligamentum flavum is frequently observed in the lower thoracic spine in both cadaver specimens 47, 263, 264,265 and plain radiographs.266, 267, 268

109 Discussion

Paradoxically, such frequency of the lesions may lead to a diagnostic pitfall in myelo- pathic patients with excessive ossification of the ligament. Second, since myelography is usually performed with the patient in prone position, defects in the posterolateral subarachnoid space may be missed. Those diagnostic difficulties are overcome by

CT as well as by metrizamide myelography in lateral and oblique views, particularly with the patient in supine position.269, 270

In ossification the ligament is replaced by mature lamellar bone and cartilage forms an ossified bridge extending from the upper and lower edges of the adjacent two laminae. 262

Unlike ossification, calcification of the ligamentum flavum tends to occur within the degenerated and thickened ligament. The calcified mass has no continuity with the lamina, and the superficial and deep layers of the ligament are relatively preserved.262

The nodular shape of such lesions seems to be specific to the ligamentum flavum271 since calcification associated with chondrocalcinosis in other parts is usually linear.272, 273

The etiology and mechanism of calcification remain unclear, but probably are distinct from those of ossification.262

Hypertrophy of LF is considered an important causative factor in the development of lumbar spinal stenosis (compression of the dural sac and roots) and significantly contributes to low back pain and sciatica.8 - 13 However there are multiple factors leading to Lumbar canal stenosis. In our study in patient no: 19 though the clinical symptoms were severe the ligamentum flavum hypertrophy was less as compared to other patients who had less symptoms so it can be stated that LF hypertrophy is not the only factor leading to lumbar canal stenosis, other factors like shape of canal, bony spurs,

110 Discussion facet joint arthropathy, spondylolisthesis and other degenerative processes are also responsible for Lumbar canal stenosis. Hence during the surgical decompression for lumbar canal stenosis the exact cause of the symptoms should be taken into account, so that the symptoms of the suffering patient are taken care of.

111 Summary and Conclusion

SUMMARY AND CONCLUSION

We have carried out a multidisciplinary study involving clinical, radiological and histological study on ligamentum flavum.

We measured the thicknesses of 180 ligamenta flava from 35 subjects in the age groups ranging from 40 to 80 years age (Mean age - 50.51 years) in Lumbar spinal stenosis group and 12 subjects in Lumbar disc herniation group in the age group ranging from 20 to 40 years (mean age - 34.33 years). Total subjects were 47.

The thickness of ligamentum flavum was found to increase with age. However, the changes with age showed spinal level dependence. The increase in thickness with age was largest at L4/L5, probably because of increased mechanical stress at this level. Al- though ligamentum flavum hypertrophy contributes significantly in spinal canal stenosis but it is not necessary that a hypertrophied ligamentum flavum will always produce spinal stenosis (symptoms) as there are other factors which also contribute to it.

In our study we also focussed on major histological changes. The following stains were used 1) Haematoxillin and Eosin stain 2) Masons Trichrome stain 3) Verhoeff stain.

The fibrosis score showed a positive linear correlation with ligamentum flavum thickness. In our histological study using Masons trichrome staining the fibrosis appeared in all ares of a hypertrophied ligamentum flavum.

In our study the histologic results with Verhoeff staining showed that the loss of elastic fibers correlated with ligamentum flavum hypertrophy. Thus it supports the theory that increased collagen (fibrosis) could be the main factor in collagen/elastin conversion without decreasing the elastic fiber content.

112 Summary and Conclusion

Our findings confirm that clinical symptoms of lumbar spinal canal stenosis are associated with calcification of the ligamentum flavum, all patients with symptoms that were considered to be severe enough to indicate decompressive surgery showed moderate to severe calcification in the ligament. Our analysis of calcification of the ligamentum flavum proves that this degenerative process can cause sciatic or neurological clinical findings in lumbar spinal stenosis. However a quantitative assessment of calcification will give better idea regarding the role of calcification in spinal stenosis.

Due to close proximity of ligamentum flavum to dura and spinal nerves, it is obvious that ligamentum flavum may contribute considerably to the pathogenesis of lumbar spinal stenosis.

Biologic assessments have also been initiated to understand further the mechanism of ligamentum flavum hypertrophy. Thus far, transforming growth factor (TGF)-ß1 is the only cytokine identified in the literature that contributes to ligamentum flavum hypertrophy.7, 18 Park et al9 found an increased level of TGF-ß1 in hypertrophied ligaments compared to the control using the enzyme-linked immunosorbent assay technique. However, an in-depth understanding of the role of TGF-ß1 on ligament hypertrophy is still lacking.

113 Summary and Conclusion

CONCLUSION:

We can conclude from our study

1. Dorsal surface which bears the maximum stress was irregular and hypertrophied

as compared to the ventral surface. The feel of the excised ligament was fibrotic

which was confirmed on histopathology.

2. Histopathology revealed predominantly fibrotic tissue and together with loss of

elastic fibres and distortion in the parallel arrangement of elastic fibres. Fibrosis

(scarring) occurs in hypertrophied ligamentum flavum, accumulation of scar tis-

sue leads to ligamentum flavum hypertrophy.

3. Calcification: Presence of calcification was constant and important finding in our

study similar to other studies in Asian population as compared to occasional and

scanty calcification in European and American population.

4. The above findings in ligamentum flavum have greatly contributed to the symp-

toms of canal stenosis in already compromised canal.

LIMITATIONS:

Following were the limitations in our study

1) Quantitative estimation of calcium.

2) Biologic Assessment: transforming growth factor (TGF) beta 1 is the only cy-

tokine identified in the literature that contributes to the ligamentum flavum

hypertrophy.

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142 Annexure

PERFORMA

NAME: AGE: SEX:

RELIGION:

ADDRESS:

CONTACT NUMBER:

REGISTRATION NO. :

OCCUPATION:

CHIEF COMPLAINTS:

HISTORY OF PRESENT ILLNESS:

PAIN: Onset

Nature

Duration

Radiation

Numbness

Weakness

Aggravating factors

Relieving factors

Previous h/o similar illness

Bowel or bladder disturbance

LIMITATION OF DAILY ACTIVITY:

Continues daily activity

Unable to work for long duration

Stopped working

CLAUDICATION:

143 Annexure

Claudication distance: (in metres)

PAST HISTORY:

DRUG HISTORY:

PERSONAL HISTORY:

SYSTEMIC EXAMINATION:

Central nervous system

Cardiovascular system:

Respiratory system:

Abdominal:

SPINE EXAMINATION:

Deformity:

Para spinal spasm :

Tenderness :

Movements – flexion

- Extension

- Lat flexion

- Rotation

Straight leg raising test (SLR):

Cross SLR:

Laseague’s sign:

Femoral stretch:

Low back pain (VAS): VAS scoring on a scale of 0 - 10 points, where 0 is no pain, 5 is moderate pain and 10 worst possible pain.

144 Annexure

0 - 10 Numerical Rating Scale

SENSORY EXAMINATION (DERMATOMAL DISTRIBUTION):

MOTOR EXAMINATION:

Hip – Flexion L R

-Extension

-Adduction

-Abduction

Knee –Flexion

-Extension

Ankle –Dorsal flexion

-Plantar flexion

EHL

EDL

FHL

FDL

REFLEXES:

Superficial: Cremastric

Anal

Deep: knee

Ankle

MRI REPORT:

145 Annexure

Level:

Vertebral body :

Disc:

Facet joint:

Ligamentum flavum:

AP canal diameter:

Lateral recess and exiting nerve root:

HISTOLOGICAL CHANGES:

MORPHOLOGICAL CHANGES:

CONSENT FORM

I ______aged

______years, resident of ______agree to participate in research work of Dr. RATNAKAR AMBADE as a subject.

Doctor has given the following information to me regarding the purpose and nature of this research work in my own language.

12. My identity will not be revealed or published anywhere without my con-

sent.

13. My examination and results of my information will be used as a data by

doctor for research purpose.

14. Doctor can use the data obtained without revealing my identity, for re-

search work and publication in future.

146 Annexure

Date: Signature/thumb impression of subject

Place:

147 Annexure

STRAIGHT LEG RAISING TEST (SLR) AND LASEGUE’S TEST:

A test to identify lumbar nerve root irritation. With both legs relaxed and knees ex- tended, the examiner will lift one leg straight up supporting the heel with the palm of the hand Test is considered positive if pain radiates below the knee joint. The angle between the leg and the examination table is then measured.

Once positive, slowly decrease in angle of leg elevation until pain disappears. At this time, dorsiflex the foot (Figure 4.40) and symptoms will redevelop confirming the nerve tension (Lasègue’s test).

This test is important if the patient’s symptoms exacerbates in 30–70° of leg elevation. Pain generated over 70° of leg elevation in most cases is not a radicular pain.

Alternatively, it can be done in a sitting position. It is performed with the patient sitting upright on the examination table and knees flexed on the edge. Active knee extension in this position often reproduces nerve root tension and pain.

FEMORAL STRETCH TEST :

This is to assess the compression on L2, L3 or L4 nerve roots. While the patient prone and knee flexed to 90°, the examiner lifts the patient’s thigh to extend the hip (Figure 4.41). Reproduction of radicular pain in anterior thigh is positive.

Alternatively it can be done in lateral position. Patient needs to lie on unaffected side with straight back, slight flexed hips and knees. Examiner will extend the knee on the affected side, and then extend the hip for 15° followed by full flexion of the knee to stretch the femoral nerve. Pain in the anterior thigh is a positive test.

148 Annexure

149 Annexure

MASTER CHART

S. Age/ Ipd. No Level Lig. Lab.Ref. Trichrome Verhoeff H & E Stain No Gender Flavum No Stain Stain (Elas- (Calcification) Thickness (Fibrosis) tic Fibres) (mm)

1 65 / F 1308140198 L4 -L5 4.45 13-5508 Grade - IV Grade – I Moderate

2 42 / M 1308210123 L4 - L5 3.875 13 - 8602 Grade – I Grade - II Minimal

3 46 / M L4 - L5 4.325 13 - 8601 Grade I Grade I Extensive

4 52 / M 130821005 L4 - L5 4.125 13 - 8600 Grade – I Grade – 0 Moderate

5 67 / M 1306100122 L4 - L5 5 13 - 8603 Grade – I Grade – 0 Moderate

6 52 / F 1306290026 L4 - L5 4.65 13 - 8604 Grade - III Grade - III Moderate

7 42 / F 130713121 L4 - L5 4.65 13 - 8599 Grade – II Grade - III Moderate

8 67 / F 14082700889 L4 - L5 4.925 13 - 8598 Grade – I Grade – 0 Minimal

9 43 / F 140624072 L4 - L5 4.95 13 - 8594 Grade - III Grade – 0 Minimal

10 42 / F 1303190045 L4 - L5 3.2 13 - 8598 Grade – I Grade – 0 No Calcification

11 41 / M 1301270114 L4 - L5 4.3 13 - 8595 Grade – I Grade – I Moderate

12 42 / M 1303180154 L4 - L5 4.875 13 - 8597 Grade – II Grade – III Extensive

13 52 / F 1310220167 L4 - L5 4.35 13 - 8592 Grade – III Grade – I Moderate

14 48 / M 1303300027 L4 - L5 5.25 13 - 8593 Grade – III Grade – I Moderate

15 50 / F 1309080013 L4 - L5 5.125 13 - 8596 Grade – III Grade – II Moderate

16 56 / F 13092330211 L4 - L5 5.5 No sample

17 48 / M 1312160106 L4 - L5 4.275 no sample

18 62 / F 1409130017 L4 - L5 4.925 no Sample

19 42 / M 1409160050 L4 - L5 3.825 14 - 12996 Grade - I ———— Minimal

20 49 / M 1503230628 L4 - L5 4.9 no sample

21 50 / M 1410070044 L4 - L5 4.675 14 - 14218 Grade - II ———— No Calcification

22 48 / F 1311040059 L4 - L5 4.8 14 - 12543 Grade – I ———— Minimal

23 59 / F 1304300126 L4 - L5 5.3 13 - 5507 Grade - IV Grade – II Moderate

24 48 / F 1304150061 L4 - L5 4.4 13 - 5503 Grade – I Grade – 0 No Calcification

25 50 / M 1311070107 L4 - L5 5.05 no sample

26 42 / M 1502200015 L4 - L5 4.025 15 - 2712 Grade – III ———— Minimal

27 44 / M 1502200038 L4 - L5 4.95 14 - 8838A Grade – I ———— Minimal

28 50 / F 1406020160 L4 - L5 4.75 14 - 8839 Grade – I ———— No

29 72 / M 1403030523 L4 - L5 5.1 no sample

30 41 / M 1409160063 L4 - L5 4.825 14 - 2128 Grade – IV ———— Extensive

31 47 / M 1411280052 L4 - L5 5.25 14 - 2129 Grade – III Grade – IV Extensive

32 41 / M 1409230013 L4 - L5 4.75 14 - 2130 Grade – III Grade – IV Extensive

33 45 / M 1503240031 L4 - L5 4.325 14 - 3983 Grade – III Grade – II Moderate

34 58 / M 1403180133 L4 - L5 4 14 - 3970 Grade – II ———— Extensive

35 65 / F 1403110015 L4 - L5 4.9 14 - 3981 Grade – III ———— Extensive

36 40 / M 1502040270 L4 -L5 2.7 14 - 2125 Grade – III Grade – I Minimal

150 Annexure

L5 - S1 3

37 30 / M 1503171524 L4 - L5 3.1 14 - 3982 Grade – II ———— Minimal

L5 - S1 2.5

38 28 / F 1503030033 L4 - L5 2.8 14 - 3972 Grade – I ———— No Calcifica- tioon

L5 -S1 3.55

39 31 / M 1504220129 L4 - L5 4.1 14 - 12544 Grade – I ———— Minimal

40 34 / M 1503200868 L5 - S1 2.7 No Sample

41 30 / F 1412030086 L4 - L5 3.75 14 - 12545 Grade – I ———— No Calcification

42 32 / F 1410280910 L4 - L5 2.8 14 - 12998 Grade – I ———— Minimal

43 35 / M 1412260032 L4 - L5 3.3 No Sample

44 40 / M 1503020992 L4 - L5 3.65 14 - 14219 Grade – II ———— No Calcification

45 38 / M 1411010055 L4 - L5 3.15 14 - 14220 Grade – II ———— No Calcification

46 40 / F 1408280139 L5 - S1 3.95 14 - 8840 Grade – I ———— No Calcification

47 34 / M 1409200083 L5 - S1 3.55 14 - 8841 Grade – I ———— No Calcification

1 – 35 Lumbar canal stenosis patients 36 – 47 Disc herniation patients.

151