a b c d Case Introduction Thirty-six-year-old patient with developmental spondylolisthesis L5/S1 Meyer- ding Grade IV. The patient initially consulted a GP with low-back pain and was treated with a brace and further conservative measures moderately success- fully over a period of 2 years. Sciatica, the beginning of neurologic deficit in the form of numbness in the left leg as well as mild vesical incontinence on sneez- ing and coughing led to presentation in our clinic. Neurologic assessment, con- ventional radiographs ( a), and MRI (b) led to the diagnosis. Posterior lumbar interbody fusion (PLIF) with placement of two PEEK cages filled with autolo- gous spongiosa was subsequently performed as a one-step procedure. An improvement of spinal realignment from Meyerding Grade IV to Meyerding Grade I–II ( c) was achieved. Postoperatively the patient had a transitory L5 weakness, which quickly improved and subsided completely after 10 days without revision surgery. One year after surgery, realignment is still held and there is bony bridging between L5 and S1 ( d). thesis.Incomparisontotheiragegroup,femaleadolescentgymnastshavea nearly four times increased probability of stress fractures of the pars interarticu- laris[40].Afurtherexampleisprofessionalbowlersandcricketplayerswho show stress lesions of the pars on the non-dominant side [84]. Even high-grade spondylolisthesis can remain asymptomatic Because even severe forms of spondylolisthesis can clinically remain completely asymptomatic, the true incidence of the condition in the general pop- ulation remains a matter of speculation. For developmental spondylolisthesis, most studies report rates of around 3%, though depending on the ethnic group assessed significantly higher incidences of up to 50% have been reported [9, 36, 42, 49, 90]. The incidence of spondylolisthesis inadultwhitemalesisreportedto be5–6%andinfemales2–3%[86].AccordingtoRocheandRowe[86],themost The incidence is 5–6% in males and 2 –3% in females frequent localization is L5–S1 in 82%, followed by L4–L5 in 11.3%, L3–L4 in 0.5% and L2–L3 in less than 0.5%. Of the acquired slippages, the degenerative type is the most frequent one. Degenerative spondylolisthesis is common in individuals older than 50 years [85]. In a radiographic study, Valkenburg and Haanen [112] showed that approximately 10% of females over 60 years of age had degenerative spondylolisthesis. Based on autopsy data, Farfan [23] found a 4.1% incidence for the condition. Previous studies have indicated that the condition occurs four times more frequently in women and is most commonly seen at L4–L5 [58]. 734 Section Spinal Deformities and Malformations Pathogenesis For a better understanding, it is worthwhile very briefly summarizing the mor- phology and biomechanics of the lumbar spine and lumbosacral joint. Put sim- ply, the spine is a two-column structure, with the anterior column consisting of vertebral bodies and discs and the posterior column composed of bony and liga- mentous structures. The sacrum acts like a bony shelf and thereby supports the proximal spinal column. The orientation of the sacrum plays a pivotal role in the development of spondylolisthesis and is influenced by pelvic rotation, hip exten- sion and lordosis [95]. Normal sacral inclination varies between 40° and 60° and the relationships between sacral slope, pelvic inclination and lumbar lordosis are High-grade isthmic spondylolisthesis is a kyphotic disorder of the lumbosacral junction dependent on the pelvic incidence, a parameter which is unique to every individ- ual [22]. A high pelvic incidence results in high shear forces at the lumbosacral junction and has been shown to be associated with an increased degree of slip- page [17, 39, 95]. Without the osteoligamentous complex of the posterior column, with the pars interarticularis acting as a bolt uniting the superior and inferior facets and the pedicle acting as a bridge to the ventral column, spinal stability would be severely compromised. To ensure that spinal stability is maintained during gait or other complex dynamic functions, an intricate interaction between the neuromuscular system, the bony and ligamentous structures as well as the viscoelastic discs is needed [30]. Spondylolysis is a result of a stress fracture of the pars interarticularis Motion is passively restricted by the ligaments and posterior facets and, depending on their orientation and size, the flexion-extension, axial rotation and lateral bending of each individual spinal segment is defined. Resistance to tor- sion depends on the integrity of facet joints and resistance to lateral bending is dependent on the integrity of the disc and the iliolumbar ligaments. Resistance to flexion is primarily dependent on the capsular ligaments of the facet joints. The disc, interspinous ligaments as well as the ligamentum flavum are only secondary flexion restraints [1]. Loads applied to the lumbosacral spine are shared between the disc and the posterior articulations [2]. While compression is resisted by the disc, shear is resisted by the disc and posterior elements as well as the stabilizing muscles [18, 110]. The effective distribution of loads shared by the posterior ele- ments and the intervertebral disc varies with posture [75]. When failure of the pars interarticularis occurs, which is usually due to a stress induced fatigue frac- ture in adolescence [120], the disc is confronted with excessive shear, flexional and rotational forces and this dissociation of the ventral from the dorsal column may subsequently result in slippage, since the anulus fibrosus cannot resist the shear forces. Spondylolisthesis is a biomechanical disorder of the entire lumbosacral junction With this very simplified morphological and biomechanical model, an attempt has been made to communicate that pathologies of the pelvis, the sacral plateau or the vertebrae themselves may be the cause of localized or even global spinal imbalance which can ultimately result in the entity of spondylolisthesis. Classification Common classification systems are those of Wiltse/Rothmann and Marchetti/Bartolozzi Due to the complex underlying pathologies which may lead to spondylolisthesis, numerous classifications have been propagated over the years [54, 56, 77, 78, 118, 119]. Of these, the two classification systems that have remained relevant are those of Wiltse and Rothman [118] and Marchetti and Bartolozzi [56] as they are applicable to all forms of lumbar spondylolisthesis and are simultaneously clini- cally relevant in terms of treatment decision [30]. While the former is an ana- tomic classification ( Table 1), the latter is etiology based (Table 2) with two main Spondylolisthesis Chapter 27 735 Table 1. Anatomic classification (according to Wiltse and Rothman [118]) Types Description I. Dysplastic In this type congenital abnormalities of the upper sacrum or the arch of L5 permit the olisthesis to occur II. Isthmic The lesion is in the pars interarticularis. Three subtypes can be recog- nized: A. Lytic failure B. Elongated but intact pars C. Acute fracture III. Degenerative Due to long-standing intersegmental instability IV. Traumatic Due to fracture in other areas of the bony hook than the pars V. Pathological There is generalized or localized bone disease Table 2. Etiology-based classification (according to Marchetti and Bartolozzi [56]) Developmental Acquired High dysplastic Traumatic Pathologic with lysis acute fracture local with elongation stress fracture systemic Low dysplastic Postsurgical Degenerative with lysis direct primary with elongation indirect secondary categories differentiating between primary developmental deficiencies and sec- ondary acquired spondylolisthesis. The Marchetti classification is almost self- explanatory and due to the avoidance of confusing terminology in our opinion seems to be more up to date. In contrast to Wiltse’s, the Marchetti classification avoids the term “isthmic” and does not differentiate between developmental and acquired forms of slip- page. Both types may have defects of the pars interarticularis, yet they present different pathologic processes [30]. Also, the term “congenital” is incorrectly used for some subtypes which develop at a later age and are not present at birth. Despite these shortcomings, the Wiltse categorization is without doubt the most frequently used and surgeons treating spinal deformities should be familiar with it. It was modified in 1989 by Wiltse and Rothmann [119] to include an extra sub- type of spondylolisthesis resulting from prior surgery. Clinical Presentation Patients with spondylolysis or spondylolisthesis may be clinically asymptomatic Patients with spondylolysis or spondylolisthesis may be asymptomatic and never present for medical evaluation. Those that seek medical advice do so with a vari- ety of symptoms. By carefully scrutinizing the information yielded by the patient, an experienced physician can draw conclusions about the underlying pathophysiologic mechanisms. History Athoroughhistoryshouldbetakenwithregardtothepain history: onset intensity quality of back pain 736 Section Spinal Deformities and Malformations Severity of spondylolisthesis does not correlate with symptoms The severity of the deformity does not always correlate with the magnitude of pain. Generally, high-grade spondylolisthesis is rarely diagnosed in adults, as many become apparent in adolescence and are then surgically managed. Patients presenting with Grade IV spondylolisthesis may be asymptomatic even though their posture is markedly distorted. There are reports of almost asymptomatic massive slippages with good sagittal balance in adults and evidence of bony sta- bilization by spontaneous fusion [33]. Make sure that the radiographically obvious pathology is the pain source Occasionally, an asymptomatic adult may develop back or radicular pain as a result of proximal lumbar disc pathology, bringing the spondylolisthesis to light for the first time. Particularly in these cases, care must be taken to ensure that the correct diagnosis is made as the spine surgeon’s attention is easily distracted by the obvious deformity present. The cardinal sy mptoms are [70]: mechanical low back pain (worse on motion, better on rest) leg pain (sciatica) Mechanical LBP may result from abnormal load distribution Mechanical back pain is thought to be due to abnormal distribution of load across the vertebral endplate following disc degeneration [63, 64]. Despite con- ventional beliefs, the hypothesis that degenerative spondylolisthesis is associated with increased motion remains to be proven. Some studies even suggest the con- trary [61, 97]. The bandwidth and intensity of pain is variable and may be of sud- den onset, chronic or intermittent. Patients may note aggravation with position transition such as changing from sitting to standing [88] and are often completelypainfreeonrest.Theleg pain can be distinguished as: referred radicular This depends on the presence of a true neural (mostly foraminal) compromise. Additional but less frequent symptoms are: discogenic back pain (worse on sitting and forward bending) facet joint pain (worse on standing and backward bending) numbness and tingling motor weakness claudication symptoms Discogenic, facet-joint and neurogenic, referred pain may coexist in spondylolisthesis Discogenic back pain can result from secondary disc degeneration in the olis- thetic or adjacent segment [37, 98]. Subsequent degenerative changes of the bone and ligamentous complex lead to spur formation, hypertrophy, subchond- ral sclerosis and destruction of the facet joints causing facet joint pain [98]. Neu- rogenic claudication is produced by spinal stenosis secondary to slippage and hypertrophy of the ligamentum flavum and facet joints encroaching into the spi- nal canal. Pain along the buttocks and both legs may occur with standing or walking and is frequently associated with dysesthesia, numbness or weakness of the legs. Most high-grade spondylolistheses become apparent during adolescence In children, the findings are very variable. In a large collective of 415 patients, Lafond [45] found that only approximately one-quarter of patients with spondy- lolysis or spondylolisthesis experienced complaints before 20 years of age, but only 9% sought medical attention during childhood or adolescence. In children, most high-grade developmental spondylolisthesis develops significant slippage during the adolescent growth period [33, 51], and this is usually when symptoms occur [36]. Several risk factors for this progression such as age, sex, spina bifida and dys- plasia have been identified [12]. Back pain in young children and adolescents always raises suspicion of an underlying spondylolysis. Adolescents with symp- Spondylolisthesis Chapter 27 737 tomatic high-grade spondylolisthesis often have sciatic pain that can develop into a sciatic crisis known as: Phalen-Dixon sign Young patients may present with a sciatic crisis known as the “Phalen-Dixon sign” This includes sciatic pain, vertical sacrum and pelvis, lumbosacral kyphosis, tight hamstrings, and an unusual pelvic waddling gait [33, 51]. This is caused by compression of the cauda equina and subsequent spasm of the ischiocrural mus- cle group. Irritation of the L5 and S1 nerve root explains sciatica. Physical Findings Patients should very carefully be neurologically assessed Physical examination should be performed to distinguish referred from radicu- lar symptoms, to document spinal sagittal alignment and spinal mobility and to establish the presence of any neurologic deficits. Particularly, the sensory and motor function needs to be checked. In the light of medicolegal issues, it seems prudent to document these findings very precisely or even refer the patient to a neurologist to document the findings. Depending on the extent of slippage, children and adolescents may present with: hyperlordosis of the lumbar spine sagittal malalignment (lumbosacral step-off) trunk deviation ( Case Study 2) flexed knee position tight hamstrings paraspinal muscle spasm gait disturbance (in high-grade spondylolisthesis) Las`egue’s sign sensorimotor deficits bowel and bladder dysfunction (very rare) Since scoliosis can be observed in conjunction with spondylolisthesis, trunk deviation and back asymmetry must be searched for. In adults and elderly patients, the physical findings often vary from those of children and rather depend on secondary segmental degeneration. Physical examination may even be unremarkable. However, frequent findings are: tight hamstrings sensorimotor deficits pain on backward bending and rotation (often facet joint pain) pain on forward bending (often discogenic pain) pain on extension from the forward bent position limitation of walking distance Pain in adults with spondylolisthesis is frequently due to secondary segmental degeneration Pain provocation on specific movements can indicate the source of the pain (e.g. facet joint or discogenic pain). However, these findings are variable and the actual prediction of the pain source is not very reliable. Yet, these signs provide a hint as to which structures should be further explored with spinal injections. Differential Diagnosis Patient radiographs and clinical presentation need to be closely correlated Degenerative spondylolisthesis may be an asymptomatic roentgenographic find- ing [98]. Belfi et al. [7] demonstrated a 5.7% prevalence of spondylolysis and a 3.1% prevalence of spondylolisthesis in asymptomatic patients. Radiographs should therefore not be overinterpreted, as numerous spinal pathologies can give rise to back and/or leg pain. Similar symptoms as found in spondylolisthesis can 738 Section Spinal Deformities and Malformations also be induced by spinal stenosis, central disc herniations or scoliotic deformi- ties. Osteoarthritis of the hip is found in about 15% of patients with degenerative Degenerative spondylolis- thesis and hip joint OA coincide in about 15 % of cases spondylolisthesis and commonly radiates to the anterior thigh and thus mimics an L3 or L4 radiculopathy [5]. Peripheral vascular disease is common in the elderly and may cause very similar symptoms to spinal claudication. Diabetic neuropathy can usually be clinically differentiated from a painful radiculopathy. As with all spinal pathologies, radiographs should be scrutinized for signs of spondylodiscitis or primary/metastatic tumor disease. Syndromes which are associated with spondylolisthesis are: neurofibromatosis I [16] Marfan syndrome [99, 122] Tricho-rhino-phalangeal syndrome [103] Ehlers-Danlos syndrome [76] myelomeningocele [101] Spondylolisthesis associated with abnormal bone and/or soft tissue constraints is rare and reports on these remain mostly anecdotal. Despite this, they should be pointed out because they can occur at unusual anatomic sites and, depending on the pathogenesis, may cause neurogenic injury as they can be high grade even with an intact neural arch [53]. Metastatic and primary bone tumors involving the spine are usually located in the vertebral body, and may of course cause significant structural weakeningoftheboneorsupportingsofttissueofthedorsalcolumn,withsubse- quent slippage of varying degrees. Less obvious are pathophysiological mecha- nisms based on a systemic bone disease. Several studies have shown that spondylo- listhesis is seen in a significant number of women with osteoporosis [107, 113, 114]. Interestingly, approximately 1/3 of the slips they identified were posterior. Appro- priate treatment of these patients, who more often than not have concomitant mas- sive degenerative changes, will depend on the amount of slippage and symptom- atology as well as the neurologic findings. The usual methods of decompression, stabilization and fusion will be indicated [53]. A further, though far rarer, example is osteogenesis imperfecta, which may lead to an elongation of pedicles or pars, and due to static moments and gravity severe slippage can occur [32, 52]. Diagnostic Work-up Imaging Standard Radiographs Search for “Scottie dog” with a collar on oblique radiographs Conventional anteroposterior and lateral radiographs should be performed as an initial assessment. In high-grade spondylolisthesis, the slipped vertebra contours a shape on the anteroposterior radiograph similar to an “inverted Napoleon’s hat” ( Fig. 1a). Very often the pars defect is already visible on the lateral view ( Fig. 1b). If a slippage or pars defect is not clearly visible, oblique (45° angled) radiographs are helpful ( Fig. 1c). In case of a pars defect, the “Scottie dog” wears acollar( Fig. 1d). Functional radiographs may give valuable information concerning spontane- ous repositioning of a slip, which may be useful in planning surgery. However, functional views have failed to reliably demonstrate an instability [25] and the motion within an olisthetic segment can even be less than in a normal segment. Meyerding’s grading of slippage is widely used A simple and easily applicable grading of the spondylolisthesis is the grading system according to Meyerding [65]. The original grading included four grades. However, it has become international convention that completely slipped verte- brae (spondyloptosis) are defined as Grade V ( Fig. 2). Spondylolisthesis Chapter 27 739 a b cd Figure 1. Radiographic findings a On the anteroposterior radiograph it appears that there are only four lumbar vertebrae, but L5 has slipped in front of S1 (spondylopto- sis) and its contour resembles an “inverted Napoleon’s hat”. b Stan- dard lateral radiograph showing a developmental (isthmic) spondy- lolisthesis L5/S1 Meyerding Grade II with a clearly visible pars defect. c Oblique radiograph showing a pars defect at the level of L4 (arrows). d Schematic drawing of the so-called “Scottie dog”. The pars defect shows up as a “collar”. Figure 2. Meyerding grading of spondylolisthesis The anteroposterior diameter of the sacrum is separated into quartiles. Slippage within the first quartile is graded as Grade I, etc., up to the fourth quartile, where it is Grade IV. Spondyloptosis is classified as Grade V. Variousmeasurementshavebeenadvocatedtocloselydescribethenormalanat- omy of the lumbosacral junction ( Fig. 3a) [12, 44, 121]. The most important mea- surements are: percent of anterior displacement ( Fig. 3b) according to Taillard [108] slip angle ( Fig. 3c) according to Boxall et al. [12] percent of rounding of top of sacrum ( Fig. 3d) 740 Section Spinal Deformities and Malformations ab cd Figure 3. Measurements of spondylolisthesis a The angle between a line across the cranial border of S1 and the horizontal plane comprises the sacrohorizontal angle. The lumbosacral angle is found by first defining the longitudinal axis of the lumbar spine, i.e. the perpendicular line to the bisector of the lumbosacral angle. The sacrohorizontal angle is formed by this line and the longitudinal axis of S1 (perpendicular line to the cranial border of S1). b The percent anterior slippage is defined as a percentage of the antero- posterior diameter of S1 according to Taillard. c The slip angle is defined by a line along the inferior border of S1 and a line perpendicular to the longitudinal axis of the sacrum. d The rounding of the sacral dome is expressed as the relation of the maximum anteroposterior diameter of the sacrum to the sacral dome [12, 121]. A high slip angle indicates progression risk The latter three measurements allow an estimation of the risk of slip progression. A high slip angle in conjunction with a rounded sacrum increases the risk of a slip progression in children. Spondylolisthesis Chapter 27 741 Bone Scans Bone scans are particularly useful in children and adolescents According to Willburger [116], bone scans are particularly valuable in children and adolescents as they allow the differentiation between acute (fresh fracture) and chronic pars defects. This has clinical implications insofar that there is a good chance of successful conservative management of a fresh pars defect or imminent stress fracture, while older lesions usually do not heal with non-opera- tive management. In adults, where acute lesions are rarely found, the sensitivity of a bone scan is poor [81]. Computed Tomography CT is of particular value if surgery is planned By means of CT, an excellent assessment of bony anatomy can be made and with evaluation of the pars interarticularis imperative information concerning the type of spondylolisthesis can be gathered. Normally, the usual gantry is angled perpendicularly to the pars defect increasing the risk of overlooking a pars defect. It is therefore recommended to angle the gantry parallel to the pars inter- articularis, i.e. perform a so-called reversed gantry CT ( Case Study 1)oruse multi-slice CT with image reformation. However, this technique is not necessary with multi-slice CT, which allows reformation of the images in the desired plane. CT scans can demonstrate a pars defect as well as facet hypertrophy and the pedi- cle anatomy (size, trajectory), which is of importance if surgery is planned. a b c d Case Study 1 A 14-year-old female presented with acute severe back pain worse on motion with tight hamstrings. Bilateral spondylolysis L4/5 was diagnosed only after a CT scan using the reversed gantry technique ( a, b) was per- formed. A bone scan demonstrated an uptake at the location of the lysis on both sides indi- cating an acute fracture (not shown). Conser- vative treatment with a lumbar brace treat- ment including the right thigh for 8 weeks was started ( c). Pain subsided very rapidly. At 4 months, the patient was symptom free. A control CT scan at 1 year postoperatively dem- onstrated healing of the acute pars fracture ( d). The patient was symptom free and regai- ned all desired activities. (Courtesy of Univer- sity Hospital Balgrist). 742 Section Spinal Deformities and Malformations a b c Figure 4. MRI characteristics of spondylolisthesis Isthmic spondylolisthesis Grade II at the level of L5/S1. a The T2-weighted image demonstrates the pseudo disc hernia- tion (black arrow), endplate (Modic) changes Type II (arrowheads) and a hyperintense zone (annular tear) in the L4/5 disc (white arrow). b The parasagittal T1-weighted image demonstrates the severe foraminal stenosis with compression of theexitingL5nerveroot(arrow). c The T2-weighted axial image demonstrates mild to moderate facet joint osteoarthritis at the L4/5 level CT is helpful for preoperative planning Placement of pedicle screws can be difficult when pedicles are dysplastic and CT is therefore helpful for preoperative planning. CT scans may also be useful in determining which cases warrant decompression in addition to fusion [59]. Sag- ittal reconstructions are helpful for exploring the adaptive changes within the olisthetic vertebrae and their subadjacent vertebrae such as the erosion and rounding off of the sacral dome in lumbosacral spondylolisthesis [44]. Magnetic Resonance Imaging If neurologic structures are compromised, MRI is the imaging modality of choice MRI easily allows the depiction of a spondylolisthesis but it is sometimes difficult to exactly localize the lysis. For the further diagnostic assessment, MRI is the method of choice. Characteristic findings in patients with spondylolisthesis are ( Fig. 4): olisthetic vertebra ( Fig. 4a) foraminal stenosis ( Fig. 4b) pseudo disc herniation ( Fig. 4a) cauda compression disc degeneration in the olisthetic and superior segment ( Fig. 4a) hyperintense zone (HIZ) in the anulus (annular tears) ( Fig. 4a) endplate abnormalities (Modic changes) ( Fig. 4a) facet joint osteoarthritis (upper adjacent level) ( Fig. 4c) tethered cord (very rare) Invasive Imaging Studies Provocative Discography This invasive method is in our opinion only justified if surgery is planned. The slipped vertebra often causes a secondary degeneration of the upper adjacent intervertebral disc. In cases with mild disc degeneration, the question arises whether the upper level should be included. In this case, provocative discography (see Chapter 10 ) can be helpful in deciding whether the upper disc level is pain- ful and should therefore be included in the fusion. Spondylolisthesis Chapter 27 743 . from radicu- lar symptoms, to document spinal sagittal alignment and spinal mobility and to establish the presence of any neurologic deficits. Particularly, the sensory and motor function needs to. sensitivity of a bone scan is poor [81]. Computed Tomography CT is of particular value if surgery is planned By means of CT, an excellent assessment of bony anatomy can be made and with evaluation of. bandwidth and intensity of pain is variable and may be of sud- den onset, chronic or intermittent. Patients may note aggravation with position transition such as changing from sitting to standing