Current Treatment Options in Neurology

, Volume 4, Issue 2, pp 147–156 | Cite as

Leptomeningeal neoplasms

  • Lauren E. Abrey

Opinion statement

Leptomeningeal metastases are a late, devastating complication of systemic cancer that typically occurs in conjunction with other systemic relapse. The most common neurologic symptoms include headache, altered mentation, and difficult walking. Diagnosis is established by neuroimaging and cerebrospinal fluid analysis. The prognosis is poor with a median survival of 6 to 8 weeks; therefore most treatment interventions are palliative. Radiotherapy should be given to sites of bulky or symptomatic tumor. Intrathecal chemotherapy is most effective in patients with lymphoma, leukemia, and breast cancer. Systemic chemotherapy may be more effective in treating bulky leptomeningeal tumor. Ventriculoperitoneal shunting can be extremely useful in patients with obstructive hydrocephalus or increased intracranial pressure.


Main Drug Interaction Cholesteatomas Leptomeningeal Metastasis Thiotepa Intrathecal Chemotherapy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References and Recommended Reading

  1. 1.
    Eberth CJ: Zur entwickelung des epitheliomas (cholesteatomas) der pia und der lung. Virchows Arch 1870, 49:51–63.Google Scholar
  2. 2.
    Siefert E: Uber die multiple Karzinomatose des Zentralnervensystems. Munch Med Wochenschr 1902, 49:826–828.Google Scholar
  3. 3.
    DeAngelis LM: Current diagnosis and treatment of leptomeningeal metastasis. J Neurooncol 1998, 38:245–252.PubMedCrossRefGoogle Scholar
  4. 4.
    Olson MD, Chernik NL, Posner JB: Infiltration of the leptomeninges by systemic cancer: a clinical and pathologic study. Arch Neurol 1974, 30:122–137.PubMedGoogle Scholar
  5. 5.
    Wasserstrom W, Glass JP, Posner JB: Diagnosis and treatment of leptomeningeal metastases from solid tumors: experience with 90 patients. Cancer 1982, 49:759–772.PubMedCrossRefGoogle Scholar
  6. 6.
    Freilich RJ, Krol G, DeAngelis LM: Neuroimaging and cerebrospinal fluid cytology in the diagnosis of leptomeningeal metastases. Ann Neurol 1995, 38:51–57.PubMedCrossRefGoogle Scholar
  7. 7.
    Schumacher M, Orszagh M: Imaging techniques in neoplastic meningiosis. J Neurooncol 1998, 38:111–120.PubMedCrossRefGoogle Scholar
  8. 8.
    Boogerd W, Hart AAM, van derSande JJ, Engelsman E: Meningeal carcinomatosis in breast cancer: prognostic factors and influence of treatment. Cancer 1991, 67:1685–1695.PubMedCrossRefGoogle Scholar
  9. 9.
    Schrappe M, Reiter A, Riehm H: Prophylaxis and treatment of neoplastic meningiosis in childhood acute lymphoblastic leukemia. J Neurooncol 1998, 38:159–165.PubMedCrossRefGoogle Scholar
  10. 10.
    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
  11. 11.
    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. Systemic methotrexate achieves therapeutic CSF levels and possibly superior results when compared with intrathecal chemotherapy.PubMedGoogle Scholar
  12. 12.
    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
  13. 13.
    Tetef ML, Margolin KA, Doroshow JH, et al.: Pharmacokinetics and toxicity of high-dose intravenous methotrexate in the treatment of leptomeningeal carcinomatosis. Cancer Chemother Pharmacol 2000, 46:19–26.PubMedCrossRefGoogle Scholar
  14. 14.
    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.PubMedCrossRefGoogle Scholar
  15. 15.
    Chamberlain MC, Kormanick PA: Neoplastic meningitis: a guide to diagnosis and treatment. CNS Drugs 1998, 10:25–41.CrossRefGoogle Scholar
  16. 16.
    Hitchins RN, Bell DR, Woods RL, Levi JA: A prospective randomized trial of single-agent versus combination chemotherapy in meningeal carcinomatosis. J Clin Oncol 1987, 5:1655–1662.PubMedGoogle Scholar
  17. 17.
    Gajjar A, Fouladi M, Walter AW, et al.: Comparison of lumbar and shunt cerebrospinal fluid specimens for cytologic detection of leptomeningeal disease in pediatric patients with brain tumors. J Clin Oncol 1999, 17:1825–1828.PubMedGoogle Scholar
  18. 18.
    Chamberlain MC, Kormanik PA: Prognostic significance of 111Indium DTPA CSF flow studies in leptomeningeal metastases. Neurology 1996, 46:1674–1677.PubMedGoogle Scholar
  19. 19.
    Mason WP, Yeh SDJ, DeAngelis LM: 111Indium-diethylenetriamine pentacetic acid cerebrospinal fluid flow studies predict distribution of intrathecally administered chemotherapy and outcome in patients with leptomeningeal metastases. Neurology 1998, 50:438–443.PubMedGoogle Scholar
  20. 20.
    Chamberlain MC. Radioisotope CSF flow studies in leptomeningeal metastases. J Neurooncol 1998, 38:135–140.PubMedCrossRefGoogle Scholar
  21. 21.
    Hannssens PEJ, Lagerwaard FJ, Levendag PC: Principles of radiotherapy of neoplastic meningitis. J Neurooncol 1998, 38:145–150.CrossRefGoogle Scholar
  22. 22.
    Sandberg DI, Bilsky MH, Souwedaine MM, et al.: Ommaya reservoirs for the treatment of leptomeningeal metastases. Neurosurgery 2000, 47:49–55. Addresses the techniques and complications associated with Ommaya reservoir placement.PubMedCrossRefGoogle Scholar
  23. 23.
    Berweiler U, Krone A, Tonn JC: Reservoir systems for intraventricular chemotherapy. J Neurooncol 1998, 38:141–143.PubMedCrossRefGoogle Scholar
  24. 24.
    Slavc I, Schuller E, Czech T, et al.: Intrathecal mafosfamide for pediatric brain tumors with meningeal dissemination. J Neurooncol 1998, 38:213–218.PubMedCrossRefGoogle Scholar
  25. 25.
    Blaney SM, Poplack DG: New cytotoxic drugs for intrathecal administration. J Neurooncol 1998, 38:219–223.PubMedCrossRefGoogle Scholar
  26. 26.
    Friedman HS, Petros W, Rich JN, et al.: Phase I trial of intrathecal Spartaject busulfan for patients with neoplastic meningitis. Proc Amer Soc Clin Oncol 2001, 20:57.Google Scholar
  27. 27.
    Chamberlain MC: A phase 2 trial of intra-CSF alpha interferon in the treatment of neoplastic meningitis. Neurology 2001, 56(suppl):A476.Google Scholar
  28. 28.
    Herrlinger U, Weller M, Schabet M: New aspects of immunotherapy of leptomeningeal metastasis. J Neurooncol 1998, 38:233–239.PubMedCrossRefGoogle Scholar
  29. 29.
    Coakham HB, Kemshead JT: Treatment of neoplastic meningitis by targeted radiation using 1311-radiolabelled monoclonal antibodies. J Neurooncol 1998, 38:225–232.PubMedCrossRefGoogle Scholar
  30. 30.
    Vrionis FD: Gene therapy of neoplastic meningitis. J Neurooncol 1998, 38:241–244.PubMedCrossRefGoogle Scholar
  31. 31.
    Stockhammer G, Poewe W, Surgstaller S, et al.: Vascular endothelial growth factor in CSF: a biological marker for carcinomatous meningitis. Neurology 2000, 54:1670–1675.PubMedGoogle Scholar
  32. 32.
    Bleyer WA: Clinical pharmacology of intrathecal methotrexate. II. An improved dosage regimen derived from age-related pharmacokinetics. Cancer Treat Rep 1977, 46:1419–1425.Google Scholar
  33. 33.
    Friedberg MH, Glantz MJ, Klempner MS, et al.: Specific matrix metalloproteinase profiles in the cerebrospinal fluid correlated with the presence of malignant astrocytomas, brain metastases and carcinomatous meningitis. Cancer 1998, 82:923–930.PubMedCrossRefGoogle Scholar
  34. 34.
    van Oostenburge RJ, Hopman AHN, Ramaekers FCS, Twijnstra A: In situ hybridization: a possible diagnostic aid in leptomeningeal metastases. J Neurooncol 1998, 38:127–133.CrossRefGoogle Scholar
  35. 35.
    Posner JB: Neurologic Complications of Cancer. Philadelphia: FA Davis Company; 1995:163.Google Scholar

Copyright information

© Current Science Inc 2002

Authors and Affiliations

  • Lauren E. Abrey
    • 1
  1. 1.Department of NeurologyMemorial Sloan-Kettering Cancer CenterNew YorkUSA

Personalised recommendations