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Semin Neurol 2021; 41(03): 291-302
DOI: 10.1055/s-0041-1725948
Review Article

Myelopathies from Neoplasms

Mary Jane Lim-Fat 
1   Division of Neurology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada
,
Jorg Dietrich
2   Division of Neuro-Oncology, Department of Neurology, Massachusetts General Hospital Cancer Center, Boston, MA
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Abstract

Benign and malignant tumors can be an important cause of myelopathy. Patients may present with a wide range of neurologic symptoms including back and neck pain, weakness, sensory abnormalities, and bowel and bladder dysfunction. Management can be challenging depending on the location and underlying biology of the tumor. Neuroimaging of the spine is an important component of diagnostic evaluation and patient management both during initial evaluation and when monitoring after treatment. This article provides a systematic and practical review of neoplasms that can cause myelopathy. Unique imaging and biological features of distinct tumors are discussed, and their management strategies are reviewed.

Keywords

myelopathy - spinal tumor - imaging - neoplasm - spine


Publication History

Article published online:
24 May 2021

© 2021. Thieme. All rights reserved.

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  • References

  • 1 Nelmes P. The Rational Clinical Examination – Evidence-Based Clinical DiagnosisThe Rational Clinical Examination – Evidence-Based Clinical Diagnosis. Nurs Stand 2013; 27 (09) 30-30
    CrossrefPubMedGoogle Scholar
  • 2 Welch WC, Erhard R, Clyde B, Jacobs GB. Systemic malignancy presenting as neck and shoulder pain. Arch Phys Med Rehabil 1994; 75 (08) 918-920
    CrossrefPubMedGoogle Scholar
  • 3 Lawson McLean AC, Rosahl SK. Growth dynamics of intramedullary spinal tumors in patients with neurofibromatosis type 2. Clin Neurol Neurosurg 2016; 146: 130-137
    CrossrefPubMedGoogle Scholar
  • 4 Samartzis D, Gillis CC, Shih P, O'Toole JE, Fessler RG. Intramedullary spinal cord tumors: part I-epidemiology, pathophysiology, and diagnosis. Global Spine J 2015; 5 (05) 425-435
    Article in Thieme ConnectPubMedGoogle Scholar
  • 5 Ostrom QT, Gittleman H, Truitt G, Boscia A, Kruchko C, Barnholtz-Sloan JS. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2011-2015. Neuro-oncol 2018; 20 (Suppl. 04) iv1-iv86
    CrossrefPubMedGoogle Scholar
  • 6 Duong LM, McCarthy BJ, McLendon RE. et al. Descriptive epidemiology of malignant and nonmalignant primary spinal cord, spinal meninges, and cauda equina tumors, United States, 2004-2007. Cancer 2012; 118 (17) 4220-4227
    CrossrefPubMedGoogle Scholar
  • 7 Van Goethem JW, van den Hauwe L, Özsarlak O, De Schepper AM, Parizel PM. Spinal tumors. Eur J Radiol 2004; 50 (02) 159-176
    CrossrefPubMedGoogle Scholar
  • 8 Villano JL, Parker CK, Dolecek TA. Descriptive epidemiology of ependymal tumours in the United States. Br J Cancer 2013; 108 (11) 2367-2371
    CrossrefPubMedGoogle Scholar
  • 9 Waldron JN, Laperriere NJ, Jaakkimainen L. et al. Spinal cord ependymomas: a retrospective analysis of 59 cases. Int J Radiat Oncol Biol Phys 1993; 27 (02) 223-229
    CrossrefPubMedGoogle Scholar
  • 10 Ebert C, von Haken M, Meyer-Puttlitz B. et al. Molecular genetic analysis of ependymal tumors. NF2 mutations and chromosome 22q loss occur preferentially in intramedullary spinal ependymomas. Am J Pathol 1999; 155 (02) 627-632
    CrossrefPubMedGoogle Scholar
  • 11 Lee C-H, Chung CK, Kim CH. Genetic differences on intracranial versus spinal cord ependymal tumors: a meta-analysis of genetic researches. Eur Spine J 2016; 25 (12) 3942-3951
    CrossrefPubMedGoogle Scholar
  • 12 Jain A, Amin AG, Jain P. et al. Subependymoma: clinical features and surgical outcomes. Neurol Res 2012; 34 (07) 677-684
    CrossrefPubMedGoogle Scholar
  • 13 Ellison DW, Kocak M, Figarella-Branger D. et al. Histopathological grading of pediatric ependymoma: reproducibility and clinical relevance in European trial cohorts. J Negat Results Biomed 2011; 10 (01) 7
    CrossrefPubMedGoogle Scholar
  • 14 Klekamp J. Spinal ependymomas. Part 1: intramedullary ependymomas. Neurosurg Focus 2015; 39 (02) E6
    CrossrefPubMedGoogle Scholar
  • 15 Abdel-Wahab M, Etuk B, Palermo J. et al. Spinal cord gliomas: a multi-institutional retrospective analysis. Int J Radiat Oncol Biol Phys 2006; 64 (04) 1060-1071
    CrossrefPubMedGoogle Scholar
  • 16 Celano E, Salehani A, Malcolm JG, Reinertsen E, Hadjipanayis CG. Spinal cord ependymoma: a review of the literature and case series of ten patients. J Neurooncol 2016; 128 (03) 377-386
    CrossrefPubMedGoogle Scholar
  • 17 Louis DN, Ohgaki H, Wiestler OD. et al. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 2007; 114 (02) 97-109
    CrossrefPubMedGoogle Scholar
  • 18 Pica A, Miller R, Villà S. et al. The results of surgery, with or without radiotherapy, for primary spinal myxopapillary ependymoma: a retrospective study from the rare cancer network. Int J Radiat Oncol Biol Phys 2009; 74 (04) 1114-1120
    CrossrefPubMedGoogle Scholar
  • 19 Louis DN, Ohgaki H, Wiestler OD, Cavenee WK. World Health Organization Histological Classification of Tumours of the Central Nervous System. France: International Agency for Research on Cancer, France; 2016
    Google Scholar
  • 20 Schiavello E, Biassoni V, Antonelli M. et al. Pediatric extraspinal sacrococcygeal ependymoma (ESE): an Italian AIEOP experience of six cases and literature review. Childs Nerv Syst 2018; 34 (07) 1291-1298
    CrossrefPubMedGoogle Scholar
  • 21 National Comprehensive Cancer Network. Central Nervous System Cancers V1.2016. 2016: 123 https://www.nccn.org/professionals/physician_gls/pdf/cns.pdf
    PubMedGoogle Scholar
  • 22 Weber DC, Wang Y, Miller R. et al. Long-term outcome of patients with spinal myxopapillary ependymoma: treatment results from the MD Anderson Cancer Center and institutions from the Rare Cancer Network. Neuro-oncol 2015; 17 (04) 588-595
    CrossrefPubMedGoogle Scholar
  • 23 Minehan KJ, Brown PD, Scheithauer BW, Krauss WE, Wright MP. Prognosis and treatment of spinal cord astrocytoma. Int J Radiat Oncol 2009; 73 (03) 727-733
    CrossrefPubMedGoogle Scholar
  • 24 Maraka S, Janku F. BRAF alterations in primary brain tumors. Discov Med 2018; 26 (141) 51-60 http://www.ncbi.nlm.nih.gov/pubmed/30265855 AccessedApril142019
    PubMedGoogle Scholar
  • 25 Collins VP, Jones DTW, Giannini C. Pilocytic astrocytoma: pathology, molecular mechanisms and markers. Acta Neuropathol 2015; 129 (06) 775-788
    CrossrefPubMedGoogle Scholar
  • 26 She DJ, Lu YP, Xiong J, Geng DY, Yin B. MR imaging features of spinal pilocytic astrocytoma. BMC Med Imaging 2019; 19 (01) 5
    CrossrefPubMedGoogle Scholar
  • 27 Teng YD, Abd-El-Barr M, Wang L, Hajiali H, Wu L, Zafonte RD. Spinal cord astrocytomas: progresses in experimental and clinical investigations for developing recovery neurobiology-based novel therapies. Exp Neurol 2019; 311: 135-147
    CrossrefPubMedGoogle Scholar
  • 28 Wu G, Broniscer A, McEachron TA. et al; St. Jude Children's Research Hospital–Washington University Pediatric Cancer Genome Project. Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas. Nat Genet 2012; 44 (03) 251-253
    CrossrefPubMedGoogle Scholar
  • 29 Solomon DA, Wood MD, Tihan T. et al. Diffuse midline gliomas with histone H3-K27M mutation: a series of 47 cases assessing the spectrum of morphologic variation and associated genetic alterations. Brain Pathol 2016; 26 (05) 569-580
    CrossrefPubMedGoogle Scholar
  • 30 Khuong-Quang D-A, Buczkowicz P, Rakopoulos P. et al. K27M mutation in histone H3.3 defines clinically and biologically distinct subgroups of pediatric diffuse intrinsic pontine gliomas. Acta Neuropathol 2012; 124 (03) 439-447
    CrossrefPubMedGoogle Scholar
  • 31 Minehan KJ, Brown PD, Scheithauer BW, Krauss WE, Wright MP. Prognosis and treatment of spinal cord astrocytoma. Int J Radiat Oncol Biol Phys 2009; 73 (03) 727-733
    CrossrefPubMedGoogle Scholar
  • 32 Westwick HJ, Giguère J-F, Shamji MF. Incidence and prognosis of spinal hemangioblastoma: a surveillance epidemiology and end results study. Neuroepidemiology 2016; 46 (01) 14-23
    CrossrefPubMedGoogle Scholar
  • 33 Deng X, Wang K, Wu L. et al. Intraspinal hemangioblastomas: analysis of 92 cases in a single institution: clinical article. J Neurosurg Spine 2014; 21 (02) 260-269
    CrossrefPubMedGoogle Scholar
  • 34 Yuan G, Liu Q, Tong D. et al. A retrospective case study of sunitinib treatment in three patients with Von Hippel-Lindau disease. Cancer Biol Ther 2018; 19 (09) 766-772
    CrossrefPubMedGoogle Scholar
  • 35 Sandalcioglu IE, Hunold A, Müller O, Bassiouni H, Stolke D, Asgari S. Spinal meningiomas: critical review of 131 surgically treated patients. Eur Spine J 2008; 17 (08) 1035-1041
    CrossrefPubMedGoogle Scholar
  • 36 Choy W, Kim W, Nagasawa D. et al. The molecular genetics and tumor pathogenesis of meningiomas and the future directions of meningioma treatments. Neurosurg Focus 2011; 30 (05) E6
    CrossrefPubMedGoogle Scholar
  • 37 Venur VA, Santagata S, Galanis E, Brastianos PK. New molecular targets in meningiomas: the present and the future. Curr Opin Neurol 2018; 31 (06) 740-746
    CrossrefPubMedGoogle Scholar
  • 38 Dasanu CA, Alvarez-Argote J, Limonadi FM, Codreanu I. Bevacizumab in refractory higher-grade and atypical meningioma: the current state of affairs. Expert Opin Biol Ther 2019; 19 (02) 99-104
    CrossrefPubMedGoogle Scholar
  • 39 Sun I, Pamir MN. Non-syndromic spinal schwannomas: a novel classification. Front Neurol 2017; 8: 318
    CrossrefPubMedGoogle Scholar
  • 40 De Verdelhan O, Haegelen C, Carsin-Nicol B. et al. MR imaging features of spinal schwannomas and meningiomas. J Neuroradiol 2005; 32 (01) 42-49
    CrossrefPubMedGoogle Scholar
  • 41 Kim P, Ebersold MJ, Onofrio BM, Quast LM. Surgery of spinal nerve schwannoma. Risk of neurological deficit after resection of involved root. J Neurosurg 1989; 71 (06) 810-814
    CrossrefPubMedGoogle Scholar
  • 42 Blakeley J, Schreck KC, Evans DG. et al. Clinical response to bevacizumab in schwannomatosis. Neurology 2014; 83 (21) 1986-1987
    CrossrefPubMedGoogle Scholar
  • 43 Fouladi M, Gajjar A, Boyett JM. et al. Comparison of CSF cytology and spinal magnetic resonance imaging in the detection of leptomeningeal disease in pediatric medulloblastoma or primitive neuroectodermal tumor. J Clin Oncol 1999; 17 (10) 3234-3237
    CrossrefPubMedGoogle Scholar
  • 44 Fischer L, Martus P, Weller M. et al. Meningeal dissemination in primary CNS lymphoma: prospective evaluation of 282 patients. Neurology 2008; 71 (14) 1102-1108
    CrossrefPubMedGoogle Scholar
  • 45 Grabb PA, Albright AL, Pang D. Dissemination of supratentorial malignant gliomas via the cerebrospinal fluid in children. Neurosurgery 1992; 30 (01) 64-71
    CrossrefPubMedGoogle Scholar
  • 46 Chen-Zhao X, Aznar-García L. Diagnosis and management of spinal metastasis of primary brain tumours. AME Case Rep 2018; 2: 26
    CrossrefPubMedGoogle Scholar
  • 47 Nor FEM, Desai V, Chew LL. Clival chordoma with drop metastases. J Radiol Case Rep 2018; 12 (03) 1-9
    Google Scholar
  • 48 Bilsky MH, Lis E, Raizer J, Lee H, Boland P. The diagnosis and treatment of metastatic spinal tumor. Oncologist 1999; 4 (06) 459-469
    CrossrefPubMedGoogle Scholar
  • 49 Schiff D, O'Neill BP. Intramedullary spinal cord metastases: clinical features and treatment outcome. Neurology 1996; 47 (04) 906-912
    CrossrefPubMedGoogle Scholar
  • 50 Payer S, Mende KC, Westphal M, Eicker SO. Intramedullary spinal cord metastases: an increasingly common diagnosis. Neurosurg Focus 2015; 39 (02) E15
    CrossrefPubMedGoogle Scholar
  • 51 Chukwueke UN, Brastianos PK. Precision medical approaches to the diagnoses and management of brain metastases. Curr Treat Options Oncol 2019; 20 (06) 49
    CrossrefPubMedGoogle Scholar
  • 52 Cole JS, Patchell RA. Metastatic epidural spinal cord compression. Lancet Neurol 2008; 7 (05) 459-466
    CrossrefPubMedGoogle Scholar
  • 53 Brook RC. K Tung RO. Batson's plexus and retrograde venous spread of malignancy – a pictorial review. Cancer Imaging 2014; 14 (Suppl. 01) 40
    CrossrefPubMedGoogle Scholar
  • 54 Laufer I, Zuckerman SL, Bird JE. et al. Predicting neurologic recovery after surgery in patients with deficits secondary to MESCC: systematic review. Spine 2016; 41 (20, Suppl 20): S224-S230
    CrossrefPubMedGoogle Scholar
  • 55 Laufer I, Rubin DG, Lis E. et al. The NOMS framework: approach to the treatment of spinal metastatic tumors. Oncologist 2013; 18 (06) 744-751
    CrossrefPubMedGoogle Scholar
  • 56 Yáñez ML, Miller JJ, Batchelor TT. Diagnosis and treatment of epidural metastases. Cancer 2017; 123 (07) 1106-1114
    CrossrefPubMedGoogle Scholar
  • 57 Kumar A, Weber MH, Gokaslan Z. et al. Metastatic spinal cord compression and steroid treatment: a systematic review. Clin Spine Surg 2017; 30 (04) 156-163
    CrossrefPubMedGoogle Scholar
  • 58 Maranzano E, Latini P. Effectiveness of radiation therapy without surgery in metastatic spinal cord compression: final results from a prospective trial. Int J Radiat Oncol Biol Phys 1995; 32 (04) 959-967
    CrossrefPubMedGoogle Scholar
  • 59 Clarke JL, Perez HR, Jacks LM, Panageas KS, Deangelis LM. Leptomeningeal metastases in the MRI era. Neurology 2010; 74 (18) 1449-1454
    CrossrefPubMedGoogle Scholar
  • 60 Boire A, Zou Y, Shieh J, Macalinao DG, Pentsova E, Massagué J. Complement component 3 adapts the cerebrospinal fluid for leptomeningeal metastasis. Cell 2017; 168 (06) 1101-1113.e13
    CrossrefPubMedGoogle Scholar
  • 61 Kaplan JG, DeSouza TG, Farkash A. et al. Leptomeningeal metastases: comparison of clinical features and laboratory data of solid tumors, lymphomas and leukemias. J Neurooncol 1990; 9 (03) 225-229
    CrossrefPubMedGoogle Scholar
  • 62 Nolan CP, Abrey LE. Leptomeningeal metastases from leukemias and lymphomas. Cancer Treat Res 2005; 125: 53-69
    CrossrefPubMedGoogle Scholar
  • 63 Clarke JL. Leptomeningeal metastasis from systemic cancer. Continuum (Minneap Minn) 2012; 18 (02) 328-342
    PubMedGoogle Scholar
  • 64 Chamberlain MC, Sandy AD, Press GA. Leptomeningeal metastasis: a comparison of gadolinium-enhanced MR and contrast-enhanced CT of the brain. Neurology 1990; 40 (3 Pt 1): 435-438
    CrossrefPubMedGoogle Scholar
  • 65 Freilich RJ, Krol G, DeAngelis LM. Neuroimaging and cerebrospinal fluid cytology in the diagnosis of leptomeningeal metastasis. Ann Neurol 1995; 38 (01) 51-57
    CrossrefPubMedGoogle Scholar
  • 66 Straathof CS, de Bruin HG, Dippel DW, Vecht CJ. The diagnostic accuracy of magnetic resonance imaging and cerebrospinal fluid cytology in leptomeningeal metastasis. J Neurol 1999; 246 (09) 810-814
    CrossrefPubMedGoogle Scholar
  • 67 Glantz MJ, Cole BF, Glantz LK. et al. Cerebrospinal fluid cytology in patients with cancer: minimizing false-negative results. Cancer 1998; 82 (04) 733-739
    CrossrefPubMedGoogle Scholar
  • 68 Chamberlain MC, Kormanik PA, Glantz MJ. A comparison between ventricular and lumbar cerebrospinal fluid cytology in adult patients with leptomeningeal metastases. Neuro-oncol 2001; 3 (01) 42-45
    PubMedGoogle Scholar
  • 69 Lamba N, Fick T, Nandoe Tewarie R, Broekman ML. Management of hydrocephalus in patients with leptomeningeal metastases: an ethical approach to decision-making. J Neurooncol 2018; 140 (01) 5-13
    CrossrefPubMedGoogle Scholar
  • 70 Kim HS, Park JB, Gwak H-S, Kwon J-W, Shin S-H, Yoo H. Clinical outcome of cerebrospinal fluid shunts in patients with leptomeningeal carcinomatosis. World J Surg Oncol 2019; 17 (01) 59
    CrossrefPubMedGoogle Scholar
  • 71 Grossman SA, Finkelstein DM, Ruckdeschel JC, Trump DL, Moynihan T, Ettinger DS. Eastern Cooperative Oncology Group. Randomized prospective comparison of intraventricular methotrexate and thiotepa in patients with previously untreated neoplastic meningitis. J Clin Oncol 1993; 11 (03) 561-569
    CrossrefPubMedGoogle Scholar
  • 72 Glantz MJ, Jaeckle KA, Chamberlain MC. et al. A randomized controlled trial comparing intrathecal sustained-release cytarabine (DepoCyt) to intrathecal methotrexate in patients with neoplastic meningitis from solid tumors. Clin Cancer Res 1999; 5 (11) 3394-3402
    PubMedGoogle Scholar
  • 73 Glantz MJ, LaFollette S, Jaeckle KA. et al. Randomized trial of a slow-release versus a standard formulation of cytarabine for the intrathecal treatment of lymphomatous meningitis. J Clin Oncol 1999; 17 (10) 3110-3116
    CrossrefPubMedGoogle Scholar
  • 74 Cachia D, Kamiya-Matsuoka C, Pinnix CC. et al. Myelopathy following intrathecal chemotherapy in adults: a single institution experience. J Neurooncol 2015; 122 (02) 391-398
    CrossrefPubMedGoogle Scholar
  • 75 Juster-Switlyk K, Smith AG, Kovacsovics T. et al. MTHFR C677T polymorphism is associated with methotrexate-induced myelopathy risk. Neurology 2017; 88 (06) 603-604
    CrossrefPubMedGoogle Scholar
  • 76 Ackermann R, Semmler A, Maurer GD. et al. Methotrexate-induced myelopathy responsive to substitution of multiple folate metabolites. J Neurooncol 2010; 97 (03) 425-427
    CrossrefPubMedGoogle Scholar
  • 77 Rock JP, Ryu S, Yin F-F, Schreiber F, Abdulhak M. The evolving role of stereotactic radiosurgery and stereotactic radiation therapy for patients with spine tumors. J Neurooncol 69 (01–3): 319-334
    CrossrefPubMedGoogle Scholar
  • 78 Allen JC, Miller DC, Budzilovich GN, Epstein FJ. Brain and spinal cord hemorrhage in long-term survivors of malignant pediatric brain tumors: a possible late effect of therapy. Neurology 1991; 41 (01) 148-150
    CrossrefPubMedGoogle Scholar
  • 79 Fein DA, Marcus Jr RB, Parsons JT, Mendenhall WM, Million RR. Lhermitte's sign: incidence and treatment variables influencing risk after irradiation of the cervical spinal cord. Int J Radiat Oncol Biol Phys 1993; 27 (05) 1029-1033
    CrossrefPubMedGoogle Scholar
  • 80 Levin VA, Bidaut L, Hou P. et al. Randomized double-blind placebo-controlled trial of bevacizumab therapy for radiation necrosis of the central nervous system. Int J Radiat Oncol Biol Phys 2011; 79 (05) 1487-1495
    CrossrefPubMedGoogle Scholar
  • 81 Calabrò F, Jinkins JR. MRI of radiation myelitis: a report of a case treated with hyperbaric oxygen. Eur Radiol 2000; 10 (07) 1079-1084
    CrossrefPubMedGoogle Scholar
  • 82 Luk KH, Baker DG, Fellows CF. Hyperbaric oxygen after radiation and its effect on the production of radiation myelitis. Int J Radiat Oncol Biol Phys 1978; 4 (5-6): 457-459
    CrossrefPubMedGoogle Scholar