major reduction in the undesirable sequelae of surgical injury with improved recovery and reduction in postoperative morbidity and overall costs. Blumenthal S, Min K, Nadig M, Borgeat A (2005)Doubleepiduralcatheterwithropiva- caineversusintravenousmorphine:acomparisonforpostoperativeanalgesiaaftersco- liosis correction surgery. Anesthesiology 102:175 – 180 In this prospective study, following scoliosis correction surgery, continuous epidural local anesthetics administered through two epidural catheters have been shown not only to provide better postoperative analgesia compared to intravenous morphine, but also to reduce side effects, improve bowel function and increase patient satisfaction. References 1. Blumenthal S, Dullenkopf A, Rentsch K, Borgeat A (2005) Continuous infusion of ropiva- caine for pain relief after iliac crest bone grafting for shoulder surgery. Anesthesiology 102:392–397 2. Blumenthal S, Min K, Nadig M, Borgeat A (2005) Double epidural catheter with ropivacaine versus intravenous morphine: a comparison for postoperative analgesia after scoliosis cor- rection operation. Anesthesiology 102:175–180 3. Blumenthal S, Borgeat A, Nadig M, Min K (2006) Postoperative analgesia after anterior cor- rection of thoracic scoliosis: a prospective randomized study comparing continuous double epidural catheter technique with intravenous morphine. Spine 31:1646–51 4. Blumenthal S, Min K, Marquardt M, Borgeat A (2007) Postoperative intravenous morphine consumption, pain scores, and side effects with perioperative oral controlled-release oxyco- done after lumbar disectomy. Anesth Analg 105:233–7 5. Boezaart AP, Eksteen JA, Spuy GV, Rossouw P, Knipe M (1999) Intrathecal morphine. Dou- ble-blind evaluation of optimal dosage for analgesia after major lumbar spinal surgery. Spine 24:1131–7 6. Carli F (1999) Perioperative factors influencing surgical morbidity: what the anesthesiolo- gistsneedtoknow.CanJAnesth46:R70–79 7. Dearborn JT, Hu SS, Tribus CB, Bradford DS (1999) Thromboembolic complications after major thoracolumbar spine surgery. Spine 24:1471–6 8. Ebraheim NA, Lu J, Yang H, Heck BE, Yeasting RA (2000) Vulnerability of the sympathetic trunk during the anterior approach to the lower cervical spine. Spine 25:1603–6 9. Fang A, Hu SS, Endres N, Bradford DS (2005) Risk factors for infection after spinal surgery. Spine 30:1460–5 10. Fujibayashi S, Shikata J, Yoshitomi H, Tanaka C, Nakamura K, Nakamura T (2001) Bilateral phrenic nerve palsy as a complication of anterior decompression and fusion for cervical ossification of the posterior longitudinal ligament. Spine 26:E281–6 11. Furnary AP, Zerr KJ, Grunkemeier GL, Starr A (1999) Continuous intravenous insulin infu- sion reduces the incidence of deep sternal wound infection in diabetic patients after cardiac surgical procedures. Ann Thorac Surg 67:352–60 12. Gajraj NM (2003) The effect of cyclooxygenase-2 inhibitors on bone healing. Reg Anesth Pain Med 28:456–65 13. Gall O, Aubineau JV, Berniere J, Desjeux L, Murat I(2001) Analgesic effect of low-dose intra- thecal morphine after spinal fusion in children. Anesthesiology 94:447–52 14. Glassman SD, Alegre G, Carreon L, Dimar JR, Johnson JR (2003) Perioperative complica- tions of lumbar instrumentation and fusion in patients with diabetes mellitus. Spine J 3: 496–501 15. Jung A, Schramm J, Lehnerdt K, Herberhold C (2005) Recurrent laryngeal nerve palsy dur- ing anterior cervical spine surgery: a prospective study. J Neurosurg Spine 2:123–7 16. Kehlet H (1994) Postoperative pain relief – what is the issue? Br J Anaesth 72:375–8 17. Kehlet H (1997) Multimodal approach to control postoperative pathophysiology and reha- bilitation. Br J Anaesth 78:606– 17 18. Kehlet H (2000) Manipulation of the metabolic response in clinical practice. World J Surg 24:690–5 19. Kurz LT, Garfin SR, Booth RE, Jr. (1989) Harvesting autogenous iliac bone grafts. A review of complications and techniques. Spine 14:1324–31 20. Mineiro J, Weinstein SL (1997) Delayed postoperative paraparesis in scoliosis surgery. A case report. Spine 22:1668–72 21. Reuben SS, Connelly NR (2000) Postoperative analgesic effects of celecoxib or rofecoxib after spinal fusion surgery. Anesth Analg 91:1221–5 22. RoderickP,FerrisG,WilsonK,HallsH,JacksonD,CollinsR,BaigentC(2005)Towardsevi- 424 Section Peri- and Postoperative Management dence-based guidelines for the prevention of venous thromboembolism: systematic reviews of mechanical methods, oral anticoagulation, dextran and regional anaesthesia as thrombo- prophylaxis. Health Technol Assess 9:1–78 23. Sagi HC,Beutler W, Carroll E,Connolly PJ (2002) Airway complications associated with sur- gery on the anterior cervical spine. Spine 27:949–53 24. Schmid RL,Sandler AN, Katz J (1999) Use and efficacy of low-dose ketamine inthe manage- ment of acute postoperative pain: a review of current techniques and outcomes. Pain 82:111–25 25. Sprung J, Abdelmalak B, Gottlieb A, Mayhew C, Hammel J, Levy PJ, O’Hara P, Hertzer NR (2000) Analysis of risk factors for myocardial infarction and cardiac mortality after major vascular surgery. Anesthesiology 93:129–40 26. Stockl B, Wimmer C, Innerhofer P, Kofler M, Behensky H (2005) Delayed anterior spinal artery syndrome following posterior scoliosis correction. Eur Spine J 14:906–9 27. Tobias JD (2004) A review of intrathecal and epidural analgesia after spinal surgery in chil- dren. Anesth Analg 98:956–65 28. van den Berghe G, Wouters P, Weekers F, Verwaest C, Bruyninckx F, SchetzM, Vlasselaers D, Ferdinande P, Lauwers P, Bouillon R (2001) Intensive insulin therapy in the critically ill patients. N Engl J Med 345:1359–67 29. Vedantam R, Lenke LG, Bridwell KH, Haas J, Linville DA (2000) A prospective evaluation of pulmonary function in patients with adolescent idiopathic scoliosis relative to the surgical approach used for spinal arthrodesis. Spine 25:82–90 Postoperative Care and Pain Management Chapter 16 425 17 Degenerative Disorders of the Cervical Spine Massimo Leonardi, Norbert Boos Core Messages ✔ Age-related changes of the cervical spine can lead to cervical spondylosis, disc herniation and spondylotic radiculopathy/myelopathy ✔ Neck pain often lacks a clear morphological correlate (i.e. is non-specific) ✔ Cervical spondylosis more frequently causes radiculopathy than disc herniation and pre- dominantly affects C5/6 and C6/7 ✔ Mechanical compression and inflammatory changes cause the clinical syndrome of radicu- lopathy ✔ Cervical spondylotic myelopathy is caused by static (spinal canal stenosis), dynamic (instabil- ity), vascular and cellular (cell injuries, apopto- sis) factors ✔ The cardinal symptom of cervical radiculopathy is radicular pain with or without a sensorimotor deficit ✔ Early symptoms of cervical myelopathy are “numb, clumsy, painful hands” and disturbance of fine motor skills. Late symptoms comprise atrophy of the interosseous muscles, gait dis- turbance, ataxia and symptoms of progressive tetraparesis ✔ The diagnostic accuracy of functional radio- graphs to reliably identify segmental instability is low. Instability remains a clinical diagnosis ✔ MRI is the imaging modality of choice for quan- tifying the extent of degenerative alterations and spinal cord compression ✔ CT myelography favorably demonstrates spurs, ossifications and foraminal stenosis in relation to the neural structures ✔ Neurophysiological studies are helpful in diag- nosing subclinical myelopathy and differentiat- ing radiculopathy from peripheral neuropathy ✔ The natural history of radiculopathy is benign while the spontaneous course of myelopathy is characterized either by long periods of stable disability followed by episodes of deterioration or a linear progressive course ✔ Scientific evidence for treatment guidelines of degenerative cervical disorders is poor ✔ Neck pain is treated non-operatively in the vast majority of patients. Indications for surgery are rare ✔ Cervical radiculopathy frequently responds favorably to conservative care. Surgery is indi- cated in patients with persistent symptoms or progressive neurological deficits ✔ The gold standard of treatment of radiculopa- thy is anterior discectomy and fusion, resulting in a favorable outcome in 80– 90% of patients ✔ Alternative methods (i.e. additional anterior plate fixation, cage fusions, total disc arthropla- sty, or minimally invasive decompressions with- outfusion)havenotbeenshowntoresultina superior outcome ✔ Mild cervical myelopathy without progression can be treated conservatively. Surgery is indi- cated in moderate to severe myelopathy. Com- plete recovery of advanced myelopathy is rare and early surgery is therefore indicated ✔ The principal aim of surgery for cervical spon- dylotic myelopathy is the decompression of the spinal cord. The surgical techniques include multilevel discectomies or corpectomies with or without instrumented fusion, laminectomy with or without instrumented fusion or lamino- plasty. ✔ The choice of technique is dependent on the target pathology and patient characteristics Degenerative Disorders Section 429 ab c d Case Introduction A 28-year-old female suffered from neck and arm pain for 3 weeks without neurological deficits. She was referred for physical therapy and manipulation. At the fourth session, the patient felt an excruciating sharp pain in her neck subse- quent to a manipulation. She was unable to stand and developed a rapidly progressive tetraparesis sub C6. The patient was referred for emergency diagnosis and treat- ment. A lateral radiograph ( a) did not show any evidence for a fracture/dislocation. MRI revealed a massive disc hernia- tion (arrow) with severe spinal cord compression (arrow- heads)atthelevelofC6/7( b, c). Immediate spinal cord decompression was prompted by anterior cervical discec- tomy, sequestrectomy and fusion (Robinson-Smith tech- nique) ( d). The patient improved rapidly after the surgery. At 1-year follow, the patient had full neurological recovery and was symptom-free. Epidemiology Degenerative alterations of the cervical spine are usually referred to as cervical spondylosis. This entity represents a mixed group of pathologies involving the intervertebral discs, vertebrae, and/or associated joints and can be due to aging (“wear and tear”, degeneration) or secondary to trauma. The predominant clini- cal symptom is neck pain, which is often associated with shoulder pain. The degenerative alterations can lead to a central or foraminal stenosis compromising nerve roots or spinal cord ( Fig. 1 ). These pathologies are termed cervical spondy- lotic radiculopathy (CSR) and cervical spondylotic myelopathy (CSM), respec- tively. CSR should be differentiated from disc herniation related radiculopathy. The annual incidence of neck pain is about 15 % In a Dutch national survey, there was an incidence of 23.1 per 1000 person- years for neck pain and 19.0 per 1000 person-years for shoulder symptoms [38]. Dutch general practitioners were consulted approximately seven times each week for a complaint relating to the neck or upper extremity; of these, three were new complaints or new episodes [38]. The annual incidence of neck pain was14.6% in a cohort of 1100 randomly selected Saskatchewan adults, 0.6% of whom devel- oped disabling neck pain [66]. Women were more likely to develop neck pain 430 Section Degenerative Disorders ab Figure 1. Cervical spondylosis a, b Age-related changes can lead to disc herniations, cervical spondylosis, osteophyte formations, facet joint osteoar- thritis, and compromise of the exiting nerve roots and the spinal cord. than men [66]. In a Swedish survey on 4415 subjects, a prevalence rate of 17% for neck pain was found. Fifty-one percent of the neck pain subjects also had chronic low back pain [108]. A history of a neck injury was reported by 25% of patients with neck pain [108]. In a prospective longitudinal investigation in France, the prevalence and incidence rates of neck and shoulder pain were assessed in an Neck pain is often associated with shoulder pain and LBP occupational setting [48]. The authors found that the prevalence (men 7.8%, women 14.8% in 1990) and incidence (men 7.3%, women 12.5% for the period 1990–1995) of chronic neck and shoulder pain increased with age, and were higher among women than men in every birth cohort examined. The disappear- ance rate of chronic neck and shoulder pain decreased with age. The paper high- lighted that adverse working conditions (e.g. repetitive work under time con- straints, awkward work for men, repetitive work for women) contributed to the development of neck and shoulder pain, independently of age [48]. The most frequent radiculopathy is C6 and C7 Cervical radiculopathy is much less frequent than neckand shoulder pain with a prevalence of 3.3 cases per 1000 people. The peak annual incidence is 2.1 cases per 1000 and it occurs in the 4thand 5th decades of life [278]. In a Sicilian popula- tion of 7653 subjects [237], a prevalence of 3.5 cases per 1000 was found for cervi- cal spondylotic radiculopathy, which increased to a peak at age 50–59 years, and decreased thereafter. The age-specific prevalence was consistently higher in women [237]. An epidemiological survey of cervical radiculopathy at the Mayo Clinic in Rochester [222] revealed that the average annual age-adjusted incidence rate per 100000 population for cervical radiculopathy was 83.2 (107.3 for males, 63.5 for females). The age-specific annual incidence rate per 100000 population reached a peak of 202.9 for the age group 50–54 years. A history of physical exer- tion or trauma preceding the onset of symptoms occurred in only 14.8% of cases. Themediandurationofsymptomspriortodiagnosiswas15days.Amono-radi- culopathy involving C7 nerve root was most frequent, followed by C6. The most frequent cause of cervical radiculopathy is spondylosis A confirmed disc protrusion was responsible for cervical radiculopathy in 21.9% of patients; in 68.4% it was related to spondylosis. During the median duration of follow-up of 4.9 years, recurrence of the condition occurred in 31.7%, Degenerative Disorders of the Cervical Spine Chapter 17 431 and 26% underwent surgery for cervical radiculopathy. At last follow-up, 90% of patients were asymptomatic or only mildly incapacitated due to cervical radicu- lopathy [222]. OPLL is a frequent cause of cervical myelopathy in Asians The epidemiology data of cervical spondylotic myelopathy have not been well explored. The aging process results in degenerative changes of the cervical spine that,inadvancedstages,cancausecompressionofthespinalcord.Itisthemost common cause of spinal cord dysfunction in the elderly [300]. A special form of cervical myelopathy is caused by the ossification of theposterior longitudinal lig- ament (OPLL). It is a multifactorial disease in which complex genetic and envi- ronmental factors interact. This disease is especially found in the Asian popula- tion[134].IntheJapanesepopulation,thereportedprevalenceraterangesfrom 1.8% to 4.1% [169, 196, 254]. The prevalence rate of OPLL in the cervical spine was significantly lower in the Chinese (0.2%) and Taiwanese populations (0.4%) [169]. A radiographic evaluation of cervical spine films at the Rizzoli Orthopae- dic Institute in Bologna, Italy, revealed a prevalence of 1.83% with a peak in the 45–64 year age group (2.83%). This prevalence was much higher than that so far reported in Caucasians [266]. Pathogenesis Age-related changes areonlyweaklycorrelated with symptoms Age-related changes of the intervertebral disc initiate the degenerative cascade and lead to a progressive deterioration of the motion segment (see Chapter 4 ). The disc height decreases leading to disc bulging as a result of progressive changes to the extracellular matrix of the disc. Microinstability results in reactive hyperostosis with formation of osteophytes at the vertebral endplates which can penetrate into the spinal canal and compromise the spinal cord and nerve roots ( Fig. 1). Osteophytes of the uncovertebral and facet joints reduce the mobility of the segment. Segmental instability leads to a hypertrophy of the yellow ligament and causes a narrowing of the spinal canal and foramen. During later stages of segmental degeneration, kyphosis of the cervical spine can occur and further compromise the spinal cord and nerve roots [250]. Although cervical spondylo- sis can lead to symptoms such as neck pain, CSR and CSM, we should bear in mind that the vast majority of changes are asymptomatic [29]. Neck Pain A morphological correlate is rarely found for neck pain The most common causes of subaxial neck pain are muscular and ligamentous factors related to improper posture, poor ergonomics and muscle fatigue [223]. The intervertebral disc and facet joints are richly innervated [51, 81, 176]. Degen- erative alterations can therefore lead to pain generation (see Chapters 4 , 5 ) representing a specific cause of neck pain. In the vast majority of cases, however, no structural correlate can be found to explain axial neck pain, i.e. neck pain most often is non-specific. Cervical Disc Herniation Disc extrusions and sequestrations tend to resorb with time Cervical radiculopathy due to disc herniation usually occurs during early stages of motion segment degeneration and mainly affects individuals in the 4th and 5th decades of life [222]. The main causes of disc herniation are age-related changesoftheintervertebraldiscmakingtheanulusfibrosussusceptibletofis- suring and tearing (see Chapter 4 ). The so-called “soft herniation” exhibits a chance for spontaneous resorption particularly in cases with disc extrusion and sequestration. Vascular supply probably plays a role in the mechanism of resorp- 432 Section Degenerative Disorders tion [177]. The phase and position of the extrusion were identified as significant factors affecting cervical disc herniation resorption [177]. Spondylotic radiculopathy is caused by mechanical and inflammatory factors The pathophysiology of radiculopathy involves both mechanic al deformation and chemical irritation of the nerve roots [232]. The release of proinflammatory cytokines and nerve growth factor (NGF) was recently identified to play a major role in the development of radicular arm pain [272]. Our current understanding of the pathogenesis of disc herniation related radiculopathy is mainly based on studies of the lumbar spine. We therefore prefer to provide a detailed overview of this issue in Chapter 18 . Cervical Spondylotic Radiculopathy Mechanical nerve root compromise is not closely related to symptoms Spondylotic radiculopathy develops during later stages of motion segment degeneration and is caused by osteophytes of the endplates, facet and uncoverte- bral joints narrowing the spinal canal and neuroforamen ( Fig. 1). These radicular entrapments (often referred to as “hard herniations”) do not spontaneously improve and usually exhibit a slowly progressing deterioration. Humphreys et al. [130] showed that in symptomatic patients foraminal heights, widths and areas are smaller than in asymptomatic controls. Foraminal stenosis can cause perma- nent or intermittent mechanical irritation of the nerve roots and can lead to hyp- oxia of the nerve root and dorsal root ganglion. The subsequent release of proin- flammatory cytokines and NGF is responsible for the generation of radicular pain [272]. Spontaneous resolution of these inflammatory processes can occur and explain why some patients can have long asymptomatic periods. This is sup- ported by the finding that the incidence of radiculopathy does not closely corre- late with age although there is an age-related increase of radiological alterations [278]. Cervical Spondylotic Myelopathy Cervical spondylosis is the most frequent cause of myelopathy in Caucasians In contrast to the lumbar spine, obliteration of the spinal canal by a disc hernia- tion or osseous spurs can lead to severe neurological deficits because of a direct compromise of the spinal cord resulting in the clinical syndrome of myelopathy. Myelopathy can result from ( Table 1): Table 1. Etiology of cervical myelopathy Acute Chronic large disc herniation cervical spondylosis traumatized narrow spinal canal ossified posterior longitudinal ligament (OPLL) CSM generally can cause a variety of neurological disturbances like spastic gait, ataxia, hyperreflexia, sensory impairment, sphincter disturbances, and motor deficit. The degree and combination of each symptom can vary extensively and there is no close relationship between the extent of compression and clinical symptoms. The pathophysiology of CSM involves [16, 32, 80]: static factors dynamic factors biologic and molecular factors Static Factors A narrow spinal canal predisposes to CSM The normal sagittal diameter of the spinal canal (C3–7) is 14–22 mm [44, 74, 119, 207] with enough space for the neural elements, ligaments and epidural fat. Degenerative Disorders of the Cervical Spine Chapter 17 433 The spinal cord occupies about three-quarters of the size of the spinal canal in the subaxial spine [80]. A narrowing of the spinal canal size can result from disc degeneration, vertebral osseous spurs, osteophyte formation at the level of the facet joints, and yellow ligament hypertrophy, calcification or ossification [205]. Patients with a congenitally narrow spinal canal (<13 mm) have a higher risk for the development of symptomatic cervical myelopathy [9, 74]. Penning et al. [209] showed that concentric compression of the cord resulted inlong tract signs only after the cross-sectional area of the cord had been reduced by about 30% to avalueofabout60mm 2 or less. This is in line with findings by Teresi et al. [267], who reported that spinal cord compression was observed in seven of 100 asymp- tomatic patients. The percentage of cord area reduction never exceeded 16% andaveragedapproximately7%.Oginoetal.[194]foundthatthedegreeofcord compromise was in good correlation with the ratio of the anteroposterior diam- eter to the transverse diameter, designated as an anteroposterior compression ratio. Dynamic Factors Instability and kyphosis aggravate CSM Dynamic compression appearstoplayamajorroleinCSM.Flexionofthecervi- cal spine causes a lengthening of the spinal cord which can be stretched over pos- terior vertebral spondylosis. In an already narrow canal this motion may damage anterior spinal cord structures [80]. Extension of the cervical spine provokes a buckling of the ligamentum flavum with dorsal compression of the spinal cord combined with anterior compression due to posterior disc bulging and/or verte- bralbodyosteophytes[80].Thisresultsinapincer effect that places the neurons of the spinal cord at great risk [40, 201, 205]. Advanced disc degeneration and height loss may allow for a translative movement with spondylolisthesis in an anterior or posterior direction decreasing the spinal canal by 2–3 mm. Loss of disc height and hypermobility of facet joints can lead to loss of lordosis and finally to ky phosis. Dynamic changes and increasing kyphosis place increased strain and shear forces on the spinal cord [16]. Biologic and Molecular Factors Corticospinal tracts are very vulnerable to ischemia Vascular factors can play a significant role in the development of myelopathy. Mechanical and vascular mechanisms can add to each other. A compressed spi- nal cord will not tolerate a diminished perfusion and a marginally vascularized cord will not tolerate compression [98, 252]. Blood supply of the different tracts in the spinal cord impacts on the pattern of ischemia and subsequent axonal degeneration. Transverse perforating vessels arising from the anterior sulcal arterial system are very susceptible to tension and likely to cause early ischemia and degeneration of the gray matter and medial white matter (anterior spinal cord syndrome) [87]. Spinal cord ischemia especially affects oligodendrocytes, which results in demyelination exhibiting features of chronic degenerative disor- ders (e.g. multiple sclerosis) [67]. Particularly the corticospinal tracts are very vulnerable and undergo early demyelination initiating the pathologic changes of cervical myelopathy [40, 80, 95, 255]. Static mechanical factors causing compression, shear and distraction and dynamic repetitive compromise are seen as primary injury whereas ischemia and the subsequent cascade at the cellular and molecular level are considered as secondary injury. These secondary mechanisms include [80, 151, 204]: glutamatergic toxicity free radical-mediated cell injury 434 Section Degenerative Disorders cationic-mediated cell injury apoptosis Secondary cellular and molecular changes further compromise spinal cord function Traumatic and ischemic injuries lead to an increase in extracellular levels of glu- tamate, which is assumed to be excitotoxic leading to neuronal death. The gener- ation of free radicals and lipid peroxidation reactions may render neurons sensi- tive to the excitotoxic effects of glutamate [80]. The failure of the Na + -K + -adeno- sine triphosphatase pump results in an accumulation of axonal Na + through non- inactivated Na + channels. The Na + channels can permit intracellular Ca 2+ entry activating enzymes (e.g. calpain, phospholipases and protein kinase C) resulting in cytoskeletal injury [80]. Apoptosis represents a fundamental biological pro- cess that contributes to the progressive neurological deficits observed in spondy- lotic cervical myelopathy [151]. A common finding of many investigations of spi- nal cord disorders is the observation that oligodendrocytes appear to be particu- larly sensitive to a wide range of oxidative, chemical, and mechanical injuries, all of which lead to oligodendrocyte apoptosis [67, 167, 255]. The early apoptotic loss of oligodendrocytes is assumed to precede axonal degeneration and partici- pate in the expression of profound and irreversible neurological deficits caused by destructive pathologic spinal cord changes under chronic mechanical com- pression seen in CSM [16, 151]. Gene polymorphism is associated with OPLL Aparticularentityistheossification of the posterior longitudinal ligament (OPLL), which particularly affects Japanese individuals and leads to a progres- sive stenosis of the cervical spinal canal and subsequently CSM [254]. OPLL is a multifactorial disease in which complex genetic as well as environmental factors play a major role [134, 282]. Gene analysis studies identified specific collagen gene polymorphisms that may be associated with OPLL, which encode for extra- cellular matrix proteins [134]. Recently, it has been shown that polymorphism of the n ucleotide pyrophosphatase (NPPS) gene plays an important role in the pathogenesis of OPLL [155, 186]. NPPS is a membrane-bound glycoprotein assumed to produce inorganic pyrophosphate which acts as a major inhibitor of calcification and mineralization. Furthermore, the involvement of many growth factors and cytokines, including bone morphogenetic proteins and transforming growth factor- , were identified in various histochemical and cytochemical anal- yses. Recent epidemiological studies confirmed an earlier finding that diabetes mellitus is a distinct risk factor for OPLL [134, 282]. Clinical Presentation Patients with a degenerative cervical disorder can present with a spectrum of symptoms ranging from benign, self-limiting neck pain to excruciating upper extremity pain with progressive severe neurological deficits. Theprimary goal of the clinical assessment is to differentiate (see Chapter 8 ): specific cervical disorders, i.e. with pathomorphological correlate non-specific cervical disorders, i.e. without evident pathomorphological correlate In specific cervical disorders a pathomorphological (structural) correlate can be found which is consistent with the clinical presentation. Accordingly, in non-spe- cific cervical disorders no such correlate can be detected. Patients can only be classified in the latter group after they have undergone a thorough clinical and diagnostic work-up. Patients frequently present with pain syndrome located in the neck-shoulder-arm region, which sometimes makes it difficult to differenti- ate neck and shoulder problems. Before the diagnosis of non-specific neck pain Degenerative Disorders of the Cervical Spine Chapter 17 435 can be made, it is mandatory to exclude differential diagnoses, e.g. shoulder pathology,or nerve entrapment syndromes. In this chapter,we focus on a pathol- ogy oriented approach. General aspects of history-taking and physical examina- tion are presented in Chapter 8 . History Differentiate neck and arm pain The predominant symptom for patients with degenerative cervical disorders is pain. Rarely, patients present with neurological symptoms without pain. The key question in differentiating the origin of patients’ pain is ( Table 2): Table 2. Key question How much of your pain is in your arm(s)/hand(s) and in your neck/shoulder(s)? In patients with predominant arm pain, the patients’ symptoms are frequently part of a radicular or myelopathic syndrome ( Table 3): Table 3. Cardinal symptoms of radiculopathy and myelopathy Radicular syndrome Myelopathic syndrome radicular pain numb, clumsy, painful hands sensory disturbances difficulty writing motor weakness disturbed fine motor skills reflex deficits difficulty walking symptoms of progressive tetraparesis (late) bowel and bladder dysfunction (late) The key finding in patients with a radicular syndrome is radicular pain,i.e.pain following a dermatomal distribution. The sensory, motor and reflex deficits are dependent on the affected nerve root. It is important to note that the pain not only radiates into the skin (dermatome) but also into the muscles (my otomes) and bone (sclerotomes)(seeChapter 8 ). Differentiation of radicular and referred arm pain is sometimes difficult The referred type of pain is sometimes difficult to differentiate from non-spe- cific radiating pain, which is not caused by a nerve root compromise. The radicu- lar pain can be preceded by neck pain which results from an incipient disc herni- ation, i.e. stretching of the anulus. Cer vical radiculopathy can be caused by a: disc herniation spondylotic stenosis Disturbed fine motor skills may indicate CSM In contrast to radiculopathy, a myelopathic syndrome can begin very subtly and can therefore pose a diagnostic challenge. The leading symptoms are numb, clumsy, painful hands [192, 198]. The examiner should particularly ask for dis- turbed fine motor skills (particularly writing skills). The degree of neck pain is largely variable. The pathoanatomical cause of the myelopathy characterizes the clinical presentation. Patients with cervical myelopathy can present with a broad spectrum of signs and symptoms. Cervical myelopathy is a clinical syndrome and dysfunction of the spinal cord, depending on the magnitude of spinal cord dysfunction and its chronicity. Early symptoms include diminished dexterity and subtle changes in balance and gait. Difficulty in manipulating small objects (e.g. buttons, needles) is typical. Myelopathy can concomitantly appear with radiculopathy since central stenosis is often combined with foraminal stenosis. In patients with predominant neck pain, the patients’ symptoms are fre- quently part of a so-called spondylotic syndrome ( Table 4). 436 Section Degenerative Disorders . hypertrophy of the yellow ligament and causes a narrowing of the spinal canal and foramen. During later stages of segmental degeneration, kyphosis of the cervical spine can occur and further compromise. which can penetrate into the spinal canal and compromise the spinal cord and nerve roots ( Fig. 1). Osteophytes of the uncovertebral and facet joints reduce the mobility of the segment. Segmental. peak of 202.9 for the age group 50–54 years. A history of physical exer- tion or trauma preceding the onset of symptoms occurred in only 14.8% of cases. Themediandurationofsymptomspriortodiagnosiswas15days.Amono-radi- culopathy