FAST FACT AND CONCEPT #135: Neoplastic Meningitis

Authors: Fareeha Siddiqui, Lisa Marr, and David Weissman

Neoplastic Meningitis (NM) a.k.a. leptomeningeal metastases, meningeal carcinomatosis or leukemic meningitis, is a common oncologic complication representing spread of tumor cells to the subarachnoid space (SAS), a complication which often portends a very short prognosis.

Epidemiology

NM is found in 20% of cancer patients at autopsy. Among solid tumors, NM is common in breast cancer, small cell lung cancer, and melanoma while rare in GI/GYN cancers. 90% of solid tumor patients with NM have widespread metastatic disease. NM is found in 40-50% of patients with hematological malignancies—mostly commonly ALL, AML and high-grade lymphomas (large cell, Burkett’s).

Signs/Symptoms

Tumor reaches the SAS by hematogenous spread via arachnoid vessels or direct invasion along nerve roots. Cancer cells in the subarachnoid space have the potential to: a) settle in dependent portions of the neuraxis (base of brain—cranial nerves, lower spinal canal); b) grow into the surface of the brain and fill the sulci and c) block normal paths of CSF flow. Thus, the hallmark of diagnosis is neurological signs/symptoms at more than one level of the neuraxis:

• Brain – headaches, nausea/vomiting, seizure, hydrocephalus
• Cranial Nerves – diplopia, hearing loss, facial numbness, dysphagia, dysphonia
• Spinal – radicular pain, weakness (usually legs), parenthesis, bladder and bowel dysfunction.

Diagnosis

CSF profile: high opening pressure, low glucose, high protein and lymphocytic pleocytosis. Sensitivity for finding malignant cells is 50- 70% for one sample increasing to 80-90% with three samples. MRI can identify nodular/bulky areas of disease, hydrocephalus and/or enhancement of the cortex/tentorium if tumor growth along the sulci leads to neovascularization. NM commonly causes abnormal CSF flow; this can be demonstrated by a radionucleotide cisternogram.

Prognosis and Treatment

Patients with breast cancer or hematological malignancies, that have not been extensively treated with chemotherapy, have a reasonable chance at remission of their CNS disease if their systemic cancer can also be controlled. In contrast, patients with other cancers (e.g. lung, melanoma) typically have a dismal prognosis (1-4 months) with or without treatment. Treatment options include chemotherapy and/or radiation. Unlike spinal cord compression or brain metastases, there is no accepted role for corticosteroids except in lymphoid malignances.

Radiation: a) Cranio-spinal irradiation (entire spinal column) or b) focused radiation therapy to sites of bulky or symptomatic areas (e.g. cauda equina for radicular leg pain).

Chemotherapy: a) systemic high-dose chemotherapy (Ara-C or Methotrexate) or b) Intrathecal (IT) chemotherapy (1-2 times per week) administered either by repeated lumbar puncture or via repeated puncture of an implanted intraventricular reservoir (e.g. Ommaya reservoir). Commonly used IT drugs include methotrexate or Ara-C.

Summary

For many patients, NM represents a pre-terminal diagnosis and no anti-neoplastic therapy is warranted. Establishing the diagnoses in such patients may be important to help prognosticate and to anticipate future neurological problems (e.g. seizures, headache, radicular pain). The decision whether or not to begin anti-neoplastic treatment should be made in consultation with a medical, radiation or neurooncologist.

References

1. Wasserstrom, WR, Glass JP and Posner JB. Diagnosis and treatment of Leptomeningeal metastases from solid tumors. Cancer 1982; 49:759-772
2. Grossman SA, Trupm DL, Chen ECP, Thopson G and Cargo EE. Cerebrospinal fluid flow abnormalities in patients with neoplastic meningitis. Am J med 1982; 73:641-647.
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.
4. Demopoulos A.et al. Leptomeningeal metastases: A review: Curr Neurol Neurosci Rep. 2004 May;4(3):196-204.

Copyright/Referencing Information : Users are free to download and distribute Fast Facts for educational purposes only. Citation for referencing: Siddiqui F and Weissman DE. Neoplastic meningitis. Fast Facts and Concepts #135: April 2005. End-of-Life/Palliative Education Resource Center www.eperc.mcw.edu.

Fast Facts were edited by David Weissman MD, Palliative Care Center, Medical College of Wisconsin until January 2007.  For comments/questions write to the current editor, Drew Rosielle MD: drosiell@mcw.edu. The complete set of Fast Facts is available at EPERC: www.eperc.mcw.edu

Disclaimer: Fast Facts provide educational information, this information is not medical advice. Health care providers should exercise their own independent clinical judgment. Some Fast Fact information cites the use of a product in dosage, for an indication, or in a manner other than that recommended in the product labeling. Accordingly, the official prescribing information should be consulted before any such product is used.

Creation Date: 4/2005

Purpose: Self-Study Guide, Teaching

Audience(s)

ACGME Competencies: Medical Knowledge, Patient Care

Keyword(s): Other neurologic disorders; Cancer

Specific Disease and Organ System Category(s): Other neurologic disorders; Cancer