PDF of Meningitis 1010

Neoplastic meningitis is an increasingly frequently occurring devastating complication of both primary CNS and extraneural malignancies. The pathologic hallmark of neoplastic meningitis is the spread of malignant cells to the CSF.1 Neurologic signs and symptoms frequently present as subtle or mild, tend to progress rapidly, and commonly result in profound morbidity and mortality. Diagnosis is often difficult, and treatment may be curative but is more often palliative as patients often have diffuse systemic disease.2,3

Neoplastic meningitis can occur at any level of the neuroaxis. The neuroaxis consists of the meninges (a three-layered, fibrous sheath that encloses the organs of the CNS), brain, spinal cord, and CSF (Figure 1). The choroid plexus produces CSF from arterial blood in the lateral and fourth ventricles of the brain at a rate of 600 to 700 ml every 24 hours.4 The average adult has approximately 140 ml of circulating CSF, 25 ml of which reside in the ventricle.4 CSF functions as a cushion and lubricant for the structures of the CNS and has roles in homeostatis and nervous system metabolism.4

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Malignant cells can gain access to the CSF and the structures of the neuroaxis through a variety of channels. Direct extension can occur from a solid tumor embedded in the brain parenchyma, or from vertebral, subdural, or epidural metastases.5 Any metastases to the choroid plexus may allow malignant cells to shed into the CSF, or spread may occur by retrograde invasion of peripheral or cranial nerves.5

The incidence of metastases to the CNS from solid tumor or hematologic malignancy has risen steadily since 1999.6 This trend could be influenced by higher success rates of treatments that result in prolonged survival for patients with extraneural cancers and by poor access to or penetration into the CNS of chemotherapies, such as large molecule targeting agents.1,5 Overall, 5% to 10% of all patients with cancer develop leptomeningeal metastasis.7 True incidence data is difficult to obtain, and neoplastic meningitis in general is thought to be underrecognized, underdiagnosed, and undertreated. In addition, health care providers may be reluctant to pursue noncurative treatment in a highly morbid disease state.


Establishing the metastatic spread of malignant cells to the CNS is in part a process of elimination. Signs and symptoms are frequently attributable to other causes.8 Currently, three methods are used to identify malignancy in the CNS: a thorough neurologic examination; MRI with and without gadolinium contrast; and CSF analysis, often of multiple samples.8 The gold standard for diagnosis is positive results on cytology of the CSF; however, any of the above methods can stand alone as diagnostic criteria. To date, entry into a clinical trial for a treatment modality requires a positive cytology result.

A thorough, systematic neurologic examination can be a powerful tool for detecting the potential presence of neoplastic meningitis. Neurologic examination is designed to assess each of the three levels of the neuroaxis, and a carefully performed examination can be used to determine the functional status of the CNS. Physical examination should be combined with careful questioning of both the patient and the caregiver.

MRI of the brain with and without contrast can demonstrate areas of suspected neoplastic disease metastasis.9 In addition, MRI can help pinpoint lesions that may be candidates for focal radiation, especially lesions that fully or partially obstruct CSF flow or produce distressing neurologic symptoms, such as weakness or radicular pain.1 MRI of the entire neuroaxis—brain and cervical, thoracic, lumbar, and sacral spine—is necessary because disease may be present in any or all of these areas regardless of observable signs or symptoms.10

The final component of the diagnostic triad is CSF analysis. Lumbar puncture is the typical method used to obtain a CSF sample and can be performed in the outpatient setting. A CSF sample can also be obtained via a ventricular access device, such as an Ommaya reservoir. The CSF is assessed for appearance (healthy fluid is clear and colorless), protein (heavy concentrations may produce a yellowish cast; normal range, 15 to 45 mg/dL), glucose (normal range, 50 to 80 mg/dL or approximately two-thirds of serum glucose), and cell count (RBC, 1,000 to 5,000/µL; WBC, 0).11,12 Cytologic examination is performed to determine the presence of malignant cells. Sample size needed for cytology is at least 10 ml of CSF, and a 3- to 5-ml sample is needed for routine studies.8 CSF sample should be fixed in preservative at the patient’s bedside because malignant cells degrade rapidly.8

Clinicians should note that findings from the diagnostic triad do not always correspond. Presence of only radiographic or cytologic evidence is common and either should be considered independently diagnostic for neoplastic disease in the CNS.10