a b c de Case Study 2 A 78-year-old man with a history of lung adenocarcinoma presented with severe mid thoracic pain and signs of cord compression in both lower extremities. Radiological assessment including plain X-rays and MRI revealed a pathological fracture of T5 with very severe cord compres- sion at the same level ( a–c). Due to limited general condi- tions, the patient was selected for a posterior approach. Large cord decompression was obtained by T5 laminec- tomy, resection of both pedicles and partial posterolateral vertebrectomy. Spinal reconstruction followed using bone cement and T4–T6 pedicular screw instrumentation ( d–e). The patient was still alive 1 year after surgery. port [1, 8]. This procedure is consequently indicated for patients with limited general health condition and life expectancy. Endovascular embolization plays a critical role in the management of certain spinal tumors. Some metastatic lesions such as renal cell or thyroid tumors are extremely hypervascular, which may result in tremendous intraoperative blood loss. Preoperative angiography and embolization offer a means of reducing the blood supply to the tumor mass, thus significantly reducing the morbidity asso- ciated with surgical resections with only a minimal complication rate [31]. This procedure is recommended to be performed within the 48 h preceding surgery. Lumbar Spine Metastatic lesions localized between L1 and L4 can be managed (tumor debul- king and spinal reconstruction) in a similar fashion to the tumors of the mid- lower thoracic spine as previously described. Depending on the location, a lateral retroperitoneal lumbotomy or a low thoracotomy with release of the diaphragm will be required to expose the lumbar spine [3, 9, 11, 35]. Metastasis of the lumbar spine can be approached from an anterior as well as a posterior approach Tumor localized in L5 can be resected through an anterior retroperitoneal or transperitoneal approach. Due to the localization, the instrumentation to the sacrum is not possible and an additional posterior fixation will complete the spi- nal reconstruction [3]. Posterolateral Vertebrectomy Posterolateral vertebrectomy with instrumentation as described for the thoracic spine can also be advocated in the lumbar spine [1, 8, 10, 24]. In this area, the 992 Section Tumors and Inflammation abcd e f gh Case Study 3 A 53-year-old woman with a history of breast cancer presented with invalidating lumbar pain. Physical examination revealed adequate general health and normal neurologic status. Radiological assessment including plain X-rays and MRI showed an L2 pathological fracture with moderate narrowing of the spinal canal ( a–c). Liver and other skeletal metasta- ses were also detected. The patient was selected for a posterior approach. Temporary pedicle screw instrumentation was first accomplished in order to stabilize the spine during decompressive laminectomy ( d, e). Bilateral pedicle resection and posterolateral vertebrectomy using pituitary rongeurs and bone curettes was carried out ( f, g). Intervertebral dis- traction using the previously inserted instrumentation allowed more radical vertebrectomy ( h). The operation was com- pleted by spinal reconstruction with bone cement, restoration of lumbar lordosis and final L1 –L3 instrumentation. debulking of the lesion will be even easier, the surgeon being able to retract the neural structures for the posterolateral resection of the tumor. Using the poste- rior instrumentation, partial reduction of the deformity caused by the pathologi- cal fracture can be obtained prior to the reconstruction of the spine using bone cement ( Case Study 3). Radical Resection and Reconstruction Radical tumor resection and spinal reconstruction is indi- cated in solitary metastasis In some rare conditions, such as patients with a solitary metastasis localized in the spine or those with an especially good prognosis (as for example indicated by a scoring system), a more radical resection of the tumor may be indicated. Spon- dylectomy is normally performed through a combined approach with a poste- rior resection of the arch and an anterior radical corpectomy using a ventrolat- eral thoracotomy or a thoracoabdominal retroperitoneal approach [18]. When reasonable survival is expected, spinal reconstruction using biological material (cage and autologous bone graft) and plate fixation is preferred. P ostoperative Patient Management One of the major goals of surgery is to improve the remaining quality of life. Therefore, surgery must allow for an early mobilization of the patient without Spinal Metastasis Chapter 34 993 rigid external fixation. In the vast majority of these cases, additional radiother- apy is performed about 2 weeks after surgery,as soon as complete wound healing is observed. In cases with previous radiotherapy, the surgeon may consider administering prophylactic antibiotics until the wound has healed to reduce the risk of infections because postoperative infections are often a detrimental com- plication which reduce life expectancy. Recapitulation Epidemiology. About two-thirds of cancer patients will develop metastases and the spineisapredom- inant area for these. Breast, lung, prostate and kid- ney are the most frequent primary tumors metasta- sizing to the spine. Pathological spine fractures are frequent with potential risks of neurologic compli- cations. Pathogenesis. The most frequent metastatic path- way is believed to be venous. Arterial, lymphatic and direct extension of the tumor are other possi- ble pathomechanisms. Spinal metastases are main- ly localized in the vertebral body and appear as osteolytic or osteoblastic lesions. They can result in vertebral body collapse, spinal instability and neu- ral compromise. Clinical presentation. Localized pain is the most common initial symptom. It is aggravated by the trunk movement, sometimes by coughing or sneez- ing. Less frequent are nerve root pain (unilateral or bilateral) and myelopathy signs due to spinal cord compression. The physical findings are often non- specific (local tenderness) unless neurologic defi- cits are present. Diagnostic work-up. All cancer patients with spinal pain require spinal imaging. Radiological signs are delayed on plain X-rays. Missing pedicle, changes in vertebral body contours, lytic lesions within verte- bral body, endplate fracture and vertebral body col- lapse are common findings. MRI is the imaging study of choice. Characteristic findings on MRI are bone marrow replacement with decreased signal on T1W and increased signal intensity on T2W im- ages, preservation of disc structure, spinal cord compression and contrast enhancement of the metastatic vertebral body. Bone scan is routinely performed to rule out bony metastases in the skele- ton but is non-specific. The identification of the primary tumor is very important and must be at- tempted in every case prior to treatment. Percuta- neous biopsy (CT guided or under image intensifier control) is reported to have a 95% accuracy rate. The most frequent primary tumors are breast (17%), lung (16%), prostate (9 %) and kidney (6%). Blood studies are non-specific. Non-operative tr eatments. The general goals of treatment are to relieve pain, reverse or prevent neurologic deficit, restore spinal stability, cure the disease (in case of a solitary metastasis) and im- prove remaining quality of life. A multidisciplinary approach involving oncologists, radiotherapists and spinal surgeons is a standard of care. Steroids are used initially in patients with acute neurologic deterioration. Radiation therapy is routinely used in symptomatic skeletal metastases and can be in- dicated in cases with radiosensitive tumors, stable or slowly progressing neurologic deficits, spinal ca- nal compromise resulting from soft tissue impinge- ment, no evidence of spinal instability, widespread spinal metastatic disease, contraindications for sur- gery or poor prognosis with short life expectancy. Radiotherapy is normally used as combined treat- ment following surgery. Operative treatment. Surgery is indicated in pa- tients with intractable pain, progressive neurologic changes, failure of radiotherapy during or after ra- diotherapy, spinal instability, cord compression or in radioresistant tumors. Decompressive laminec- tomy alone is rarely indicated. The goals of surgical intervention are better accomplished combining decompression of neural structures, debulking of tumor mass, realignment of spinal deformity and spinal reconstruction with instrumentation. Differ- ent anterior or posterior approaches are possible and will depend on location and extent of neural impingement, number of vertebrae involved, re- gion of the spine affected, need for spinal stabiliza- tion and the patient’s medical condition. 994 Section Tumors and Inflammation Key Articles Tokuhashi Y, Matsuzaki H, Hiroshi O, et al. (2005)Arevisedscoringsystemforpreoper- ative evaluation of metastatic spine tumor prognosis. Spine 30:2186 –2191 Clinical and radiological assessment of patients with spinal metastases. Preoperative classification system with guidelines for surgery and prognosis. Wise J, Fischgrund J, Herkowitz H, et al. (1999)Complications,survivalrates,andrisk factors of surgery for metastatic disease of the spine. Spine 24:1943 – 1951 Retrospective study analyzing risk factors for surgical complications. A relatively long survival time after spinal surgery and a low rate of major complications justify surgical treatment. Careful preoperative selection is discussed. Bilsky M, B oland P, Lis E, et al. (2000) Single-stage posterolateral transpedicle approach forspondylectomy,epiduraldecompressionandcircumferentialfusionofspinalmetas- tases. Spine 17:2240 –2250 Retrospective study and a good description of the surgical technique for posterolateral vertebrectomy and spinal reconstruction. The authors demonstrate the feasibility of the techniquewithalowcomplicationrateandnoneedforICUinthepostoperativefollow- up. Gokaslan Z, York J, Walsh G, et al. (1998) Transthoracic vertebrectomy for metastatic spinal tumors. J Neurosurg 89:599 – 609 Article reporting the surgical technique for radical vertebrectomies in the thoracic spine. Indications and complications are reported in a retrospective study. 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(2000) Single-stage posterolateral transpedicle approach for spondylectomy, epidural decompression and circumferential fusion of spinal metastases. Spine 17:2240–2250 9. Boland P, Lane J, Sundaresan N (1982) Metastatic disease of the spine. Clin Orthop 169: 95–104 10. Bridwell K, Jenny A, Saul T, et al. (1988) Posterior segmental spinal instrumentation with posterolateral decompression and debulking for metastatic thoracic and lumbar spine dis- ease: limitation of the technique. Spine 13:1383–1394 11. Brihaye J, Ectors P, Lemort M, et al. (1988) The management of spinal epidural metastases. Adv Tech Stand Neurosurg 16:121–129 12. Bünger C, Laursen M, Hansen E, et al. (1999) A new algorithm for the surgical treatment of spinal metastases. Spine 24:101–105 13. Coman D, De Long R, Mc Cucheon J (1951) Studies on the mechanism of metastasis: the dis- tribution of tumors in various organs in relation to the distribution of arterial emboli. Can- cer Res 11:648 14. Deramond H, Depriester C, Galibert P, Le Gars D (1988) Percutaneous vertebroplasty with polymethylmethacrylate. Radiol Clinics North Am 36:533–546 15. Edelstyn G, Gillespie P, Grebbel F (1967) The radiological demonstration of osseous metas- tases: experimental observation. Clin Radiol 18:158 16. Emery S, Brazinski M, Koka A, et al. (1994) The biological and biomechanical effects of irradiation on anterior spinal bone grafts in a canine model. J Bone Joint Surg 76(A):540– 548 Spinal Metastasis Chapter 34 995 17. Galasko C (1986) Skeletal metastases. Clin Orthop 210:18–25 18. Gokaslan Z, York J, Walsh G, et al. (1998) Transthoracic vertebrectomy for metastatic spinal tumors. J Neurosurgery 89:599–609 19. Harrington K (1986) Metastatic disease of the spine. J Bone Joint Surg 68A:1110– 1115 20. Harrington K (1997) Orthopaedic surgical management of skeletal complications. Cancer 80:1614–1627 21. Jansson K, Bauer H (2006) Survival complication and outcome in 282 patients operated for neurological deficit due to thoracic or lumbar spinal metastases. Eur Spine J 15:196–202 22. Joo K, Parthasaranthy K, Bakshi S, et al. (1979) Bone scintigrams: their clinical usefulness in patients with breast carcinoma. Oncology 36:94–99 23. Karnofsky D (1967) Clinical evaluation of anti-cancer drugs: cancer chemotherapy. GANN Monogr 2:223–231 24. Magerl F, Coscia M (1988) Total posterior vertebrectomy of the thoracic or lumbar spine. Clin Orthop 232:62–69 25. Marchesi D, Boos N, Aebi M (1993) Surgical treatment of tumors of the cervical spine and first two thoracic vertebrae. J Spinal Disord 6:489–496 26. Mink J (1986) Percutaneous bone biopsy in the patient with known or suspected osseous metastases. Radiology 161:191–195 27. Murphy W, Destonet J, Gilula L (1981) Percutaneous skeletal biopsy: a procedure for radiol- ogists – results, review and recommendations. Radiology 139:545–561 28. Nottebaert M, von Hochstetter A, Exner G, et al. (1987) Metastatic carcinoma of the spine. Int Orthop 11:345–348 29. Oda I, Abumi K, Ito M, et al. (2006) Palliative spinal reconstruction using cervical pedicle screws for metastatic lesions of the spine. Spine 31:1439–1444 30. O’Mara R (1974) Bone scanning in osseous metastatic disease. JAMA 229:1915–1918 31. Prabhu V, Bilsky M, Jambhekar K, et al. (2003) Results of preoperative embolization for met- astatic spinal neoplasms. J Neurosurg Spine 2:156–164 32. Schaberg J, Gainor B (1985) A profile of metastatic carcinoma of the spine. Spine 10:19–26 33. Tokuhashi Y, Matsuzaki H, Toriyama S, et al. (1990) Scoring system for the preoperative evaluation of metastatic spine tumor prognosis. Spine 15:1110–1113 34. Tokuhashi Y, Matsuzaki H, Hiroshi O, et al. (2005) A revised scoring system for preoperative evaluation of metastatic spine tumor prognosis. Spine 30:2186–2191 35. Tomita K, Kawahara N, Kobayashi T, et al. 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Spine 24:1943 –1951 996 Section Tumors and Inflammation 35 Intradural Tumors Yashuhiro Yonekawa, Richard Marugg Core Messages ✔ Intradural spinal tumors can be classified into extramedullary tumors (tumors that are inside the dura but outside the spinal cord – approxi- mately 65 % of cases) and intramedullary tumors (tumors within the spinal cord tissue – approximately 35% of cases) ✔ The majority of intradural extramedullary tumors (80%) are meningiomas and nerve sheath tumors (neurinomas and neurofibromas) ✔ Intradural intramedullary tumors are frequently (60 %) ependymomas and astrocytomas ✔ MRI is the diagnostic method of choice ✔ Introduction of the microsurgical technique has greatly improved surgical results ✔ Intraoperative ultrasound localization or navi- gation can be helpful, while intraoperative neu- rophysiological monitoring still needs to be refined for credible use ✔ Most extramedullary tumors can be resected totally. For intramedullary tumor a gross total resection can be achieved in ependymomas, hemangioblastomas and cavernous angiomas with a clear cleavage plane between the tumor and normal spinal cord tissue. This is not usu- ally the case in astrocytomas ✔ Consideration should always be given to whether the spine has been rendered unstable by the pathology or by surgical intervention Epidemiology Successful removal of a spinal tumor was first reported by Horsely in 1888 [15]. Elsberg proposed a two-stage operation in the case of intramedullary tumors lacking a definitive plane between the spinal cord and tumor in the early part of the twentieth century [12, 13], albeit with high morbidity and mortality. With new technological advances especially the introduction of the bipolar coagulator and microsurgery, starting in the 1950s and 1960s respectively [16, 17, 21], the surgical risks were dramatically reduced. Intradural tumors especially intramedullary tumors are rare and are most often slow-growing tumors Intradural tumors represent about 10% of primary central nervous system (CNS) tumors, and about two-thirds of these tumors are in an extramedullary location. Around 80% of extramedullary tumors are meningiomas and nerve sheath tumors (neurinomas and neurofibromas). Fifteen percent of extramed- ullary tumors are ependymomas of the filum terminale in the conus cauda region. Although the filum terminale is of neuroectodermal origin, these tumors are often categorized as extramedullary from the anatomical and surgi- cal point of view. Rare tumors such as paragangliomas, drop metastases or granulomas represent the remaining 5% [9]. Intramedullary tumors are uncommon and the incidence is below 1 per 100000 population. Most of them are slow-growing neoplasms. More than 60% of all spinal cord tumors are glio- mas, e.g., ependymomas ( Case Introduction ) and astrocytomas. Around 70% of tumors are located in the cervical or upper thoracic part of the spinal cord [3, 14, 20]. Tumors and Inflammation Section 997 abcd Case Introduction A 32-year-old woman presented with a 9-month history of complaints. In the last pregnancy trimenon she complained about paresthesias in the right leg with an increasing weakness of both legs. Just after the normal delivery, she had a complete paraplegia for 5 min. Three months later she noticed paresthesia in the left hand, followed by a bandlike pain- ful dysesthesia radiating to the chest and weakness in both arms. The MRI of the spine showed an intradural intramedul- lary tumor ( a, c). The cervical cord is enlarged at both ends of the solid tumor component, which shows a contrast enhancement. At the caudal end of the tumor a cyst is visible. The signal behavior of the cyst is similar to cerebrospinal fluid and at the rostral end multicystic formations are visible. At both ends of the tumor there are hydromyelia and exten- sive edema. The tumor was grossly radically resected by posterior midline longitudinal myelotomy (for surgical treat- ment see Fig. 5). The histopathologic diagnosis was ependymoma (WHO grade 1). The patient showed no additional postoperative deficits; the motor function was intact. Postoperative MRI ( b, d) shows the cervical spinal cord after tumor resection. At the time of follow-up 3 months later, the patient showed normal motor function but complained of girdle- like dysesthesia at the chest radiating into the small finger on the left side. Multiplicity of extramedullary tumors and their association with intramedullary tumors is typical for patients with neurofibromatosis [24, 38]. Etiology and Pathogenesis Some neoplasms appear to be the result of genetic disease The etiology of intradural tumors remains unclear, but there is now considerable evidence that some neoplasms are the result of genetic disease. Genetic studies of tumors are focused on chromosomal aberrations, the role of mitogenic differen- tiation factors and their surface receptors, growth factors, oncogenes and tumor suppressor genes. Multiple meningiomas in combination with bilateral acoustic neurinomas establish the diagnosis of neurofibromatosis Type 2 (NF-2). An NF disorder should be considered even in patients with solitary meningioma or nerve sheath tumor. Between 35% and 45% of patients with nerve root tumors have neurofibromatosis. Intramedullary tumors are common in NF-2 ( Fig. 1 ). These are typically ependymomas. NF-2 is associated with an abnormality on chro- mosome 22 [24, 38]. Spinal hemangioblastomas occur in 30% of patients with von Hippel-Lindau disease, which is associated with an abnormality on chro- mosome 3 [31]. 998 Section Tumors and Inflammation ab c Figure 1. Neurofibromatosis Type 2 A patient with neurofibromatosis Type II. a, b Different intradural extramedullary (meningiomas and neurofibromas) and intradural intramedullary tumors (ependymoma) as well as c extraspinal tumors are to be seen in the whole spine. Disorders associated with intradural spinal tumors are neurofibro- matosis Type 2 and von Hippel-Lindau disease For unknown reasons most intramedullary tumors are benign, in contrast to brain tumors. The spinal cord has an enor- mous functional adaptabil- ity to slowly growing com- pressive tumors Often an extensive perilesional edema can be found in a caudal and rostral direction, which is considered to be due to impaired venous return in the pres- enceofthespecialanatomyofthevalvelessvenousplexus[27].Around70%of intramedullary tumors are accompanied by syringo- or hydromyelia and/or intramedullary cyst formation. There is an enormous functional adaptability of the spinal cord tissue to compression of slow-growing tumors, so that the average reported duration between the onset of symptomatology and the diag- nosis has been reported to be as long as 3.5 years. Neurological impairment is produced mainly by compression of the tissue rather than by tumor invasion [31]. Classification of Intradural Tumors Intradural-Extramedullary Tumors Meningiomas Meningiomas frequently occur in the thoracic spine and in females The arachnoid cap cells or immature fibroblasts of the dura are considered to be the tumor precursor cells. Most meningiomas are found entirely intradurally. However, transdural growth or entirely extradural growth is also possible. Inva- sive growth or hyperostotic reaction of the bone is rare. Tumors are predomi- nantly found in the thoracic spine. The tumor attachment is often lateral with a ventral or dorsal extension. Symptomatology is very insidious The upper cervical spine and the foramen magnum are also common sites. Meningiomas of this location often occupy a ventral or ventrolateral position and may adhere to the vertebral artery near its intradural entry and initial intracra- nial course [1, 4, 33, 35]. The ratio of spinal to intracranial meningiomas is about 1:8; the mean age at presentation is 56 years. More than 80% of spinal meningio- mas occur in women [24, 35]. Multiple spinal meningiomas are rare. Meningio- Intradural Tumors Chapter 35 999 mas in the region of the conus and cauda equina are uncommon, representing only 2% of all spinal cord meningiomas. Due to the predilection for the thoracic location and above-mentioned functional adaptability of the spinal cord, clinical symptoms are very insidious. A complete removal of spinal meningiomas is achieved in the vast majority of cases with a recurrence rate of less than 10%. Aggressive meningiomas and malignant upgrading of spinal meningiomas are extremely rare [24, 35]. Nerve Sheath Tumors Two main types are found in the spine: neurinoma (schwannoma or neurilemoma) neurofibroma Nerve sheath tumors occur at every level of the spinal canal The proliferating cell is the Schwann cell. Neurinomas (Case Study 1)arewell- circumscribed intradural or extradural or combined intra-extradural tumors starting either from the nerve sheaths of peripheral nerves or spinal nerve roots or peripheral nerves. Their occurrence can be sporadic or can be within the scopeofNF-2orlessfrequentlyofNF-1[7,9,25,38].Mostaresolitaryanddis- tributed equally over the whole spinal canal level. Peak incidence is around the 5th decade. Males and females are equally affected. Most nerve sheath tumors are intradural. Around 10% of tumors extend through the dural root sleeve, comprising the so-called “dumbbell” type. Most nervesheathtumorsderivefromadorsalnerveroot,whileventralnerveroot tumors are neurofibromas. Nerve sheath tumors can mimic the symptoms of disc herniations The clinical symptoms are often indistinguishable from those associated with disc herniation: pain and radiculopathy, followed by paresthesias and limb weak- ness. Spinal cord compression can result in myelopathic symptoms. A sarcoma- tous transformation has been reported to occur in up to 11% of patients with neurofibromatosis [31]. Filum Terminale Ependymoma From the anatomical and surgical perspective this tumor is often categorized as extramedullary in location, although it should be classified as an intramedullary tumor, since the filum terminale is of neuroectodermal origin. Astrocytomas, oligodendrogliomas and paragangliomas can also originate in the filum termi- nale. Myxopapillary ependymoma is the most common histologic type [30]. Paraganglioma Paragangliomas are rare tumors that are found in the cauda equina and filum ter- minale [37]. Differential Diagnosis Differential diagnosis includes rare non-neoplastic causes of diffuse nerve root enlargement or thickening such as: toxic neuropathy inflammatory neuritis sarcoidosis ( Fig. 2a) histiocytosis spinal intradural malignant metastasis ( Fig. 2b, c) 1000 Section Tumors and Inflammation ab c d e Case Study 1 A 40-year-old woman noticed gait disturbance of abrupt onset with motor weakness of the right lower limb and a sen- sory impairment below the level of T6 but without sphincter disturbances. Since 2 years previously she had suffered from progressive thoracic pain. Since 1 year previously the thoracic back pain had worsened associated with paresthesias in both legs, more on the right side. Fifteen and 8 years previously, she had microdiscectomies at the level of L4/5 and L5/S1. Due to a tachyarrythmia a heart pacemaker was implanted at the age of 20 years. Therefore a myelography and a myelo-CT were performed as the diagnostic method of choice instead of the contraindicated MRI. The myelography ( a, b) demon- strated the tumor and the cord contour and the contrast block at the level of the caudal tumor pole at T8. The CT scan after the myelography presented an intradural-extramedul- lary tumor on the right side at thoracic level 6– 8 with an enor- mous compression of the spinal cord ( c, d). A laminectomy at three levels was performed and a neurinoma (WHO grade 1) was totally removed (for surgical treatment see Fig. 4). The sensory roots at the level were partly sacrificed. The post- operative sagittal reconstructed CT scan ( e) of the thoracic region demonstrated laminectomies, tumor removal and the contour of the spinal cord without any signs of compression. Two days after surgery the motor weakness of the lower extremity was improved so that she could ambulate without aid. At 12 months follow-up she had no back pain and a nor- mal gait but still had a sensory disturbance at the thoracic level due to the sacrificed dorsal roots. Intradural Tumors Chapter 35 1001 . the disease (in case of a solitary metastasis) and im- prove remaining quality of life. A multidisciplinary approach involving oncologists, radiotherapists and spinal surgeons is a standard of care. Steroids are. indicated. The goals of surgical intervention are better accomplished combining decompression of neural structures, debulking of tumor mass, realignment of spinal deformity and spinal reconstruction. approaches are possible and will depend on location and extent of neural impingement, number of vertebrae involved, re- gion of the spine affected, need for spinal stabiliza- tion and the patient’s