Neoplastic meningitis

Article

Abstract

Neoplastic meningitis (NM) occurs in approximately 5% of all patients with cancer. NM is a disease affecting the entire neuraxis, so staging and treatment need to encompass all cerebrospinal fluid (CSF) compartments. Central nervous system staging of NM includes contrast-enhanced brain and spine imaging and radionuclide CSF flow study. Treatment of NM incorporates involved-field radiotherapy of bulky or symptomatic disease sites and intra-CSF drug therapy. The inclusion of concomitant systemic therapy may benefit patients with NM and may obviate the need for intra-CSF chemotherapy. At present, intra-CSF drug therapy is confined to three chemotherapeutic agents (ie, methotrexate, cytosine arabinoside, and thiotepa) administered on a variety of schedules either by intralumbar or intraventricular drug delivery. Although treatment of NM is palliative, with an expected median patient survival of 3 to 6 months, it often affords stabilization and protection from further neurologic deterioration in patients with NM.

Keywords

Neoplastic Meningitis Meningeal Carcinomatosis Entire Neuraxis Ogic Sign 

References and Recommended Reading

  1. 1.
    Shapiro WR, Posner JB, Ushio Y, et al.: Treatment of meningeal neoplasms. Cancer Treat Rep 1977, 61:733–743.PubMedGoogle Scholar
  2. 2.
    Nugent JL, Bunn PA Jr, Matthews MJ, et al.: CNS metastases in small cell bronchogenic carcinoma: increasing frequency and changing pattern with lengthening survival. Cancer 1979, 44:1885–1893.PubMedCrossRefGoogle Scholar
  3. 3.
    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, 9:225–229.PubMedCrossRefGoogle Scholar
  4. 4.
    Siegal T, Lossos A, Pfeffer MR: Leptomeningeal metastases: analysis of 31 patients with sustained off-therapy response following combined-modality therapy. Neurology 1994, 44:1463–1469.PubMedGoogle Scholar
  5. 5.
    Chamberlain MC: Carcinomatous meningitis. Arch Neurol 1997, 54:16–17.PubMedGoogle Scholar
  6. 6.
    Glass JP, Melamed M, Chernik NL, et al.: Malignant cells in cerebrospinal fluid (CSF): the meaning of a positive CSF cytology. Neurology 1979, 29:1369–1375.PubMedGoogle Scholar
  7. 7.
    Wasserstrom WR, Glass JP, Posner JB: Diagnosis and treatment of leptomeningeal metastases from solid tumors: experience with 90 patients. Cancer 1982, 49:759–772.PubMedCrossRefGoogle Scholar
  8. 8.
    Little JR, Dale AJ, Okazaki H: Meningeal carcinomatosis. Clinical manifestations. Arch Neurol 1974, 30:138–143.PubMedGoogle Scholar
  9. 9.
    Rosen ST, Aisner J, Makuch RW, et al.: Carcinomatous leptomeningitis in small cell lung cancer: a clinicopathologic review of the National Cancer Institute experience. Medicine (Baltimore) 1982, 61:45–53.CrossRefGoogle Scholar
  10. 10.
    Amer MH, AlSarraf M, Baker LH, et al.: Malignant melanoma and central nervous system metastases: incidence, diagnosis, treatment and survival. Cancer 1978, 42:660–668.PubMedCrossRefGoogle Scholar
  11. 11.
    Yap HY, Yap BS, Tashima CK, et al.: Meningeal carcinomatosis in breast cancer. Cancer 1978, 42:283–286.PubMedCrossRefGoogle Scholar
  12. 12.
    van Oostenbrugge RJ, Twijnstra A: Presenting features and value of diagnostic procedures in leptomeningeal metastases. Neurology 1999, 53:382–385.PubMedGoogle Scholar
  13. 13.
    Balm M, Hammack J: Leptomeningeal carcinomatosis. Presenting features and prognostic factors. Arch Neurol 1996, 53:626–632.PubMedGoogle Scholar
  14. 14.
    Sorensen SC, Eagan RT, Scott M: Meningeal carcinomatosis in patients with primary breast or lung cancer. Mayo Clin Proc 1984, 59:91–94.PubMedGoogle Scholar
  15. 15.
    Gonzalez-Vitale JC, Garcia-Bunuel R: Meningeal carcinomatosis. Cancer 1976, 37:2906–2911.PubMedCrossRefGoogle Scholar
  16. 16.
    Grossman SA, Krabak MJ: Leptomeningeal carcinomatosis. Cancer Treat Rev 1999, 25:103–119.PubMedCrossRefGoogle Scholar
  17. 17.
    Chamberlain MC: Radioisotope CSF flow studies in leptomeningeal metastases. J Neurooncol 1998, 38:135–140.PubMedCrossRefGoogle Scholar
  18. 18.
    Boyle R, Thomas M, Adams JH: Diffuse involvement of the leptomeninges by tumour—a clinical and pathological study of 63 cases. Postgrad Med J 1980, 56:149–158.PubMedGoogle Scholar
  19. 19.
    Wolfgang G, Marcus D, Ulrike S: Leptomeningeal carcinomatosis: clinical syndrome in different primaries. J Neurooncol 1998, 38:103–110.PubMedCrossRefGoogle Scholar
  20. 20.
    Chamberlain MC, Kormanik PR: Carcinomatous meningitis secondary to breast cancer: predictors of response to combined modality therapy. J Neurooncol 1997, 35:55–64.PubMedCrossRefGoogle Scholar
  21. 21.
    Kolmel HW: Cytology of neoplastic meningosis. J Neurooncol 1998, 38:121–125.PubMedCrossRefGoogle Scholar
  22. 22.
    Murray JJ, Greco FA, Wolff SN, et al.: Neoplastic meningitis. Marked variations of cerebrospinal fluid composition in the absence of extradural block. Am J Med 1983, 75:289–294.PubMedCrossRefGoogle Scholar
  23. 23.
    Rogers LR, Duchesneau PM, Nunez C, et al.: Comparison of cisternal and lumbar CSF examination in leptomeningeal metastasis. Neurology 1992, 42:1239–1241.PubMedGoogle Scholar
  24. 24.
    Chamberlain MC, Kormanik PA, Glantz MJ: A comparison between ventricular and lumbar cerebrospinal fluid cytology in adult patients with leptomeningeal metastases. Neuro-oncology 2001, 3:42–45.PubMedGoogle Scholar
  25. 25.
    Glantz MJ, Cole BF, Glantz LK, et al.: Cerebrospinal fluid cytology in patients with cancer: minimizing false-negative results. Cancer 1998, 82:733–739.PubMedCrossRefGoogle Scholar
  26. 26.
    DeAngelis LM: Current diagnosis and treatment of leptomeningeal metastasis. J Neurooncol 1998, 38:245–252.PubMedCrossRefGoogle Scholar
  27. 27.
    Wasserstrom WR, Schwartz MK, Fleisher M, et al.: Cerebrospinal fluid biochemical markers in central nervous system tumors: a review. Ann Clin Lab Sci 1981, 11:239–251.PubMedGoogle Scholar
  28. 28.
    Van Zanten AP, Twijnstra A, Hart AA, et al.: Cerebrospinal fluid lactate dehydrogenase activities in patients with central nervous system metastases. Clin Chim Acta 1986, 161:259–268.PubMedCrossRefGoogle Scholar
  29. 29.
    Klee GG, Tallman RD, Goellner JR, et al.: Elevation of carcinoembryonic antigen in cerebrospinal fluid among patients with meningeal carcinomatosis. Mayo Clin Proc 1986, 61:9–13.PubMedGoogle Scholar
  30. 30.
    Twijnstra A, van Zanten AP, Hart AA, et al.: Serial lumbar and ventricle cerebrospinal fluid lactate dehydrogenase activities in patients with leptomeningeal metastases from solid and haematological tumours. J Neurol Neurosurg Psychiatry 1987, 50:313–320.PubMedGoogle Scholar
  31. 31.
    Stockhammer G, Poewe W, Burgstaller S, et al.: Vascular endothelial growth factor in CSF: a biological marker for carcinomatous meningitis. Neurology 2000, 54:1670–1676.PubMedGoogle Scholar
  32. 32.
    Chamberlain MC: Cytologically negative carcinomatous meningitis: usefulness of CSF biochemical markers. Neurology 1998, 50:1173–1175.PubMedGoogle Scholar
  33. 33.
    Garson JA, Coakham HB, Kemshead JT, et al.: The role of monoclonal antibodies in brain tumour diagnosis and cerebrospinal fluid (CSF) cytology. J Neurooncol 1985, 3:165–171.PubMedCrossRefGoogle Scholar
  34. 34.
    Hovestadt A, Henzen-Logmans SC, Vecht CJ: Immunohistochemical analysis of the cerebrospinal fluid for carcinomatous and lymphomatous leptomeningitis. Br J Cancer 1990, 62:653–654.PubMedGoogle Scholar
  35. 35.
    Boogerd W, Vroom TM, van Heerde P, et al.: CSF cytology versus immunocytochemistry in meningeal carcinomatosis. J Neurol Neurosurg Psychiatry 1988, 51:142–145.PubMedCrossRefGoogle Scholar
  36. 36.
    Van Oostenbrugge RJ, Hopman AH, Ramaekers FC, et al.: In situ hybridization: a possible diagnostic aid in leptomeningeal metastasis. J Neurooncol 1998, 38:127–133.PubMedCrossRefGoogle Scholar
  37. 37.
    Cibas ES, Malkin MG, Posner JB, et al.: Detection of DNA abnormalities by flow cytometry in cells from cerebrospinal fluid. Am J Clin Pathol 1987, 88:570–577.PubMedGoogle Scholar
  38. 38.
    Biesterfeld S, Bernhard B, Bamborschke S, et al.: DNA single cell cytometry in lymphocytic pleocytosis of the cerebrospinal fluid. Acta Neuropathol (Berl) 1993, 86:428–432.CrossRefGoogle Scholar
  39. 39.
    Van Oostenbrugge RJ, Hopman AH, Arends JW, et al.: The value of interphase cytogenetics in cytology for the diagnosis of leptomeningeal metastases. Neurology 1998, 51:906–908.PubMedGoogle Scholar
  40. 40.
    Rhodes CH, Glantz MJ, Glantz L, et al.: A comparison of polymerase chain reaction examination of cerebrospinal fluid and conventional cytology in the diagnosis of lymphomatous meningitis. Cancer 1996, 77:543–548.PubMedCrossRefGoogle Scholar
  41. 41.
    Cheng TM, O’Neill BP, Scheithauer BW, et al.: Chronic meningitis: the role of meningeal or cortical biopsy. Neurosurgery 1994, 34:590–595.PubMedCrossRefGoogle Scholar
  42. 42.
    Chamberlain MC, Sandy AD, Press GA: Leptomeningeal metastasis: a comparison of gadolinium-enhanced MR and contrast-enhanced CT of the brain. Neurology 1990, 40:435–438.PubMedGoogle Scholar
  43. 43.
    Schumacher M, Orszagh M: Imaging techniques in neoplastic meningiosis. J Neurooncol 1998, 38:111–120.PubMedCrossRefGoogle Scholar
  44. 44.
    Sze G, Soletsky S, Bronen R, et al.: MR imaging of the cranial meninges with emphasis on contrast enhancement and meningeal carcinomatosis. AJR Am J Roentgenol 1989, 153:1039–1049.PubMedGoogle Scholar
  45. 45.
    Schuknecht B, Huber P, Buller B, et al.: Spinal leptomeningeal neoplastic disease. Evaluation by MR, myelography and CT myelography. Eur Neurol 1992, 32:11–16.PubMedCrossRefGoogle Scholar
  46. 46.
    Chamberlain MC: Comparative spine imaging in leptomeningeal metastases. J Neurooncol 1995, 23:233–238.PubMedCrossRefGoogle Scholar
  47. 47.
    Freilich RJ, Krol G, DeAngelis LM: Neuroimaging and cerebrospinal fluid cytology in the diagnosis of leptomeningeal metastasis. Ann Neurol 1995, 38:51–57.PubMedCrossRefGoogle Scholar
  48. 48.
    Mittl RL Jr, Yousem DM: Frequency of unexplained meningeal enhancement in the brain after lumbar puncture. AJNR Am J Neuroradiol 1994, 15:633–638.PubMedGoogle Scholar
  49. 49.
    Glantz MJ, Hall WA, Cole BF, et al.: Diagnosis, management, and survival of patients with leptomeningeal cancer based on cerebrospinal fluid-flow status. Cancer 1995, 75:2919–2931.PubMedCrossRefGoogle Scholar
  50. 50.
    Grossman SA, Trump CL, Chen DC, et al.: Cerebrospinal flow abnormalities in patients with neoplastic meningitis. Am J Med 1982, 73:641–647.PubMedCrossRefGoogle Scholar
  51. 51.
    Chamberlain MC, Kormanik PA: Prognostic significance of 111indium-DTPA CSF flow studies in leptomeningeal metastases. Neurology 1996, 46:1674–1677.PubMedGoogle Scholar
  52. 52.
    Mason WP, Yeh SD, DeAngelis LM: 111Indium-diethylenetriamine pentaacetic acid cerebrospinal fluid flow studies predict distribution of intrathecally administered chemotherapy and outcome in patients with leptomeningeal metastases. Neurology 1998, 50:438–444.PubMedGoogle Scholar
  53. 53.
    Chamberlain MC, Corey-Bloom J: Leptomeningeal metastases: 111indium-DTPA CSF flow studies. Neurology 1991, 41:1765–1769.PubMedGoogle Scholar
  54. 54.
    Chamberlain MC, Kormanik P, Jaeckle KA, et al.: 111Indium-diethylenetriamine pentaacetic acid CSF flow studies predict distribution of intrathecally administered chemotherapy and outcome in patients with leptomeningeal metastases. Neurology 1999, 52:216–217.PubMedGoogle Scholar
  55. 55.
    Hildebrand J: Prophylaxis and treatment of leptomeningeal carcinomatosis in solid tumors of adulthood. J Neurooncol 1998, 38:193–198.PubMedCrossRefGoogle Scholar
  56. 56.
    Chamberlain MC, Kormanik PA: Prognostic significance of coexistent bulky metastatic central nervous system disease in patients with leptomeningeal metastases. Arch Neurol 1997, 54:1364–1368.PubMedGoogle Scholar
  57. 57.
    Chamberlain MC: Neoplastic meningitis-related encephalopathy: prognostic significance. Neurology 2003, 60:A17–A18.CrossRefGoogle Scholar
  58. 58.
    Shapiro WR, Young DF, Mehta BM: Methotrexate: distribution in cerebrospinal fluid after intravenous, ventricular and lumbar injections. N Engl J Med 1975, 293:161–166.PubMedGoogle Scholar
  59. 59.
    Berweiler U, Krone A, Tonn JC: Reservoir systems for intraventricular chemotherapy. J Neurooncol 1998, 38:141–143.PubMedCrossRefGoogle Scholar
  60. 60.
    Sandberg DI, Bilsky MH, Souweidane MM, et al.: Ommaya reservoirs for the treatment of leptomeningeal metastases. Neurosurgery 2000, 47:49–54.PubMedCrossRefGoogle Scholar
  61. 61.
    Sause WT, Crowley J, Eyre HJ, et al.: Whole brain irradiation and intrathecal methotrexate in the treatment of solid tumor leptomeningeal metastases—a Southwest Oncology Group study. J Neurooncol 1988, 6:107–112.PubMedCrossRefGoogle Scholar
  62. 62.
    Chamberlain MC, Kormanik P: Carcinoma meningitis secondary to non-small cell lung cancer: combined modality therapy. Arch Neurol 1998, 55:506–512.PubMedCrossRefGoogle Scholar
  63. 63.
    Siegal T: Leptomeningeal metastases: rationale for systemic chemotherapy or what is the role of intra-CSF-chemotherapy? J Neurooncol 1998, 38:151–157.PubMedCrossRefGoogle Scholar
  64. 64.
    Giannone L, Greco FA, Hainsworth JD: Combination intraventricular chemotherapy for meningeal neoplasia. J Clin Oncol 1986, 4:68–73.PubMedGoogle Scholar
  65. 65.
    Hitchins RN, Bell DR, Woods RL, et al.: A prospective randomized trial of single-agent versus combination chemotherapy in meningeal carcinomatosis. J Clin Oncol 1987, 5:1655–1662.PubMedGoogle Scholar
  66. 66.
    Grossman SA, Finkelstein DM, Ruckdeschel JC, et al.: Randomized prospective comparison of intraventricular methotrexate and thiotepa in patients with previously untreated neoplastic meningitis. J Clin Oncol 1993, 11:561–569.PubMedGoogle Scholar
  67. 67.
    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, 5:3394–3402.PubMedGoogle Scholar
  68. 68.
    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, 17:3110–3116.PubMedGoogle Scholar
  69. 69.
    Jaeckle KA, Batchelor T, O’Day SJ, et al.: An open trial of sustained-release cytarabine (Depocyt) for the intrathecal treatment of solid tumor neoplastic meningitis. J Neurooncol 2002, 57:231–239.PubMedCrossRefGoogle Scholar
  70. 70.
    Siegal T, Pfeffer MR, Steiner I: Antibiotic therapy for infected Ommaya reservoir systems. Neurosurgery 1988, 22(1 Pt 1):97–100.PubMedGoogle Scholar
  71. 71.
    Kerr JZ, Berg S, Blaney SM: Intrathecal chemotherapy. Crit Rev Oncol Hematol 2001, 37:227–236.PubMedCrossRefGoogle Scholar
  72. 72.
    Bleyer WA, Drake JC, Chabner BA: Neurotoxicity and elevated cerebrospinal-fluid methotrexate concentration in meningeal leukemia. N Engl J Med 1973, 289:770–773.PubMedGoogle Scholar
  73. 73.
    Bokstein F, Lossos A, Siegal T: Leptomeningeal metastases from solid tumors: a comparison of two prospective series treated with and without intra-cerebrospinal fluid chemotherapy. Cancer 1998, 82:1756–1763.PubMedCrossRefGoogle Scholar
  74. 74.
    Glantz MJ, Cole BF, Recht L, et al.: High-dose intravenous methotrexate for patients with nonleukemic leptomeningeal cancer: is intrathecal chemotherapy necessary? J Clin Oncol 1998, 16:1561–1567.PubMedGoogle Scholar
  75. 75.
    Boogerd W, Dorresteijn LD, van der Sande JJ, et al.: Response of leptomeningeal metastases from breast cancer to hormonal therapy. Neurology 2000, 55:117–119.PubMedGoogle Scholar
  76. 76.
    Blaney SM, Poplack DG: New cytotoxic drugs for intrathecal administration. J Neurooncol 1998, 38:219–223.PubMedCrossRefGoogle Scholar
  77. 77.
    Sampson JH, Archer GE, Villavicencio AT, et al.: Treatment of neoplastic meningitis with intrathecal temozolomide. Clin Cancer Res 1999, 5:1183–1188.PubMedGoogle Scholar
  78. 78.
    Herrlinger U, Weller M, Schabet M: New aspects of immunotherapy of leptomeningeal metastasis. J Neurooncol 1998, 38:233–239.PubMedCrossRefGoogle Scholar
  79. 79.
    Coakham HB, Kemshead JT: Treatment of neoplastic meningitis by targeted radiation using 131I-radiolabelled monoclonal antibodies. J Neurooncol 1998, 38:225–232.PubMedCrossRefGoogle Scholar
  80. 80.
    Vrionis FD: Gene therapy of neoplastic meningiosis. J Neurooncol 1998, 38:241–244.PubMedCrossRefGoogle Scholar
  81. 81.
    Rubenstein JI, Fridlyand J, Abrey L, et al.: Phase 1 study of intraventricular administration of rituximab in patients with recurrent CNS and intraocular lymphoma. J Clin Oncol 2007, 25:1350–1356.PubMedCrossRefGoogle Scholar
  82. 82.
    Chamberlain MC, Wei-Tao DD, Groshen S: A phase 2 trial of intra-CSF etoposide in the treatment of neoplastic meningitis. Cancer 2006, 31:2021–2027.CrossRefGoogle Scholar
  83. 83.
    Chamberlain MC: Alpha-interferon in the treatment of neoplastic meningitis. Cancer 2002, 94:2675–2680.PubMedCrossRefGoogle Scholar
  84. 84.
    Shapiro WR, Schmid M, Glantz M, Miller JJ: A randomized phase III/IV study to determine benefit and safety of cytarabine liposome injection for treatment of neoplastic meningitis [abstract]. J Clin Oncol 2006, 24(Suppl):1528.CrossRefGoogle Scholar
  85. 85.
    Boogerd W, van den Bent MJ, Koehler PJ, et al.: The relevance of intraventricular chemotherapy for leptomeningeal metastasis in breast cancer: a randomized study. Eur J Cancer 2004, 40:2726–2733.PubMedCrossRefGoogle Scholar

Copyright information

© Current Medicine Group LLC 2008

Authors and Affiliations

  1. 1.Department of Neurology, Fred Hutchinson Cancer Research CenterUniversity of Washington Neuro-Oncology ProgramSeattleUSA

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