Elsevier

The Lancet Neurology

Volume 5, Issue 5, May 2006, Pages 443-452
The Lancet Neurology

Review
Neoplastic meningitis

https://doi.org/10.1016/S1474-4422(06)70443-4Get rights and content

Summary

Neoplastic meningitis is a complication of the CNS that occurs in 3–5% of patients with cancer and is characterised by multifocal neurological signs and symptoms. Diagnosis is problematic because the disease is commonly the result of pleomorphic manifestations of neoplastic meningitis and co-occurrence of disease at other sites. Useful tests to establish diagnosis and guide treatment include MRI of the brain and spine, cerebrospinal fluid (CSF) cytology, and radioisotope CSF flow studies. Assessment of the extent of disease of the CNS is of value because large-volume subarachnoid disease or CSF flow obstruction is prognostically significant. Radiotherapy is an established and beneficial treatment for patients with neoplastic meningitis with large tumour volume including parenchymal brain metastasis, sites of symptomatic disease, or CSF flow block. Because neoplastic meningitis affects the entire neuraxis, chemotherapy treatment can include intra-CSF fluid (either intraventricular or intralumbar) or systemic therapy. Most patients (>70%) with neoplastic meningitis have progressive systemic disease and consequently treatment is palliative and tumour response is of restricted durability. Furthermore, as there is no compelling evidence of a survival advantage with aggressive multimodal treatment, future trials need be done to determine the effect of treatment on quality of life and control of neurological symptoms.

Introduction

Neoplastic meningitis is reported in patients with solid tumours (carcinomatous meningitis), haematological malignancies (leukaemic or lymphomatous meningitis), or primary brain tumours. Neoplastic meningitis results from the spread of malignant cells to the leptomeninges and subarachnoid space and dissemination of tumour cells within the cerebrospinal fluid (CSF) compartment. Early diagnosis is important because fixed neurological deficits rarely respond to treatment and furthermore, early treatment of neoplastic meningitis prevents progressive neurological injury that substantially impairs quality of life.

Section snippets

Epidemiology

The incidence of neoplastic meningitis varies according to the tumour site. It occurs in 3% of patients with breast cancer (range 0·8–5%), 6% of those with small-cell lung cancer, 1% with non-small cell lung cancer, 0·015–0·25% with gastrointestinal tumours, 3% with unknown primary tumours, and 1·5% with melanoma.1, 2, 3, 4, 5, 6, 7 In primary brain tumours the prevalence of neoplastic meningitis varies from <1–10% depending upon tumour histology.8, 9, 10, 11, 12

Lymphomatous meningitis is

Anatomy and pathogenesis

An energy-dependent process produces CSF in the choroid plexus of the third, fourth, and lateral ventricles. CSF circulates in a defined pattern within the CNS (figure 1), has a total volume of 140 cm3 that is established by age 3–5 years, and has a total volume turnover time of about 8 h.

Tumour cells reach the subarachnoid space either through the blood (venous or arterial), by growing along nerve and vascular sheaths, or by migration from a tumour adjacent to CSF (parenchymal brain

Symptoms and signs of the disease

After reaching the subarachnoid space and leptomeninges, tumour cells are transported by the CSF to all regions of the CNS and thereby involve the entire neuraxis. As a consequence, 52% (range 9–76%) of patients present with pleomorphic and multifocal neurological symptoms and signs that vary according to CNS territory involved (cranial nerves, spine, and cerebrum) (table 1).8, 22, 23, 24, 25, 26, 27, 28

Headache, alteration of mentation, and ataxia are the leading cerebral symptoms and are seen

MRI

MRI is more sensitive for the assessment of the brain than is CT.29, 30 However, MRI is similar in quality to CT myelography for assessment of the spine in patients with neoplastic meningitis. Standard MRI assessment of patients with neoplastic meningitis should include both the brain and spine to examine the entire neuraxis because bulky sites of disease might require additional treatment (figure 2).

On MRI, leptomeningeal enhancement is a contrast-enhancing layer that can extend into the sulci

Prognosis and therapy

Treatment of neoplastic meningitis aims to extend survival and stabilise or improve neurological symptoms. Most untreated patients die within 1–9 weeks (median 3 weeks) as a result of neurological disease and tumour progression.4, 22, 28, 45

Early diagnosis is important becuase patients who present with few or no neurological deficits and a low CNS tumour burden commonly achieve a better treatment response and improved survival. Negative prognostic factors (panel 2)46, 47, 48, 49, 50, 51, 52, 53

Conclusions

Only seven prospective randomised trials of neoplastic meningitis have been done, some with contradictory results.5, 45, 46, 48, 52, 68, 90, 95 Therefore a clear consensus regarding treatment remains problematic and consequently no standard therapy exists. The National Cancer Cancer Network treatment guidelines provide useful suggestions regarding treatment.96 Very few studies of neoplastic meningitis have been tumour-type specific. The therapeutic approach commonly differs when comparing

Search strategy and selection criteria

A MEDLINE search was done between January 1985 and December 2005 using the following key words: “meningeosis”, “neoplastic meningitis”, “carcinomatous meningitis”, “leukemic meningitis”, “lymphomatous meningitis”, “leptomeningeal metastasis”, “CSF”, and “CSF cytology”. Only articles in English were considered and only case series or trials (randomised or not) were analysed. Literature citations were reviewed for authenticity. Case reports were excluded.

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