Malignant meningitis is defined as the diffuse involvement of leptomeninges by infiltrating malignant cells. It is called leptomeningeal carcinomatosis
if the primary is a solid tumour, and lymphomatous meningitis
or leukaemic meningitis
if the primary is not a solid tumour. Although malignant meningitis occurs in approximately 5–18% of lung cancer patients, the sole manifestation of malignant meningitis in cancer is unusual and most cancer patients have active systemic disease.1,2
It is a well recognised complication in specific malignant tumours which can include lung cancer, breast cancer, melanoma, lymphomas and leukaemias.3,4
In lung cancer, the most common types are small cell and adenocarcinoma.
Signs and symptoms of malignant meningitis depend on which part of the nervous system is involved. Symptoms are usually multifocal and more diffuse than can be explained by one discrete lesion. Careful physical examination may reveal numerous neurological abnormalities.
Although identification of malignant cells in the CSF is diagnostic, initial tests may be falsely negative in up to 50% of patients with malignant meningitis.5
CSF sensitivity increases to 80%6
with repeated lumbar puncture, which should be done if strong clinical suspicion or CSF analysis showed hypo-glycorachia (low glucose in the spinal fluid). Path physiology is not clear but more acceptable theories are either rapid utilisation of glucose by malignant cells or blockade of the barrier between the blood and the cerebrospinal fluid.7
When a diagnosis of malignant meningitis is suspected, a brain imaging study should be performed first. MRI is the preferred method. If MRI is not immediately available, a CT of the brain with intravenous contrast should be performed before the lumbar puncture. Abnormalities include hydrocephalus, or enhancement of the cerebral sulci or cistern on contrast enhanced CT scan.4
However, the CT scan may be normal in 18–44% of patients with malignant meningitis.4
Before the advent of central nervous system (CNS) prophylaxis irradiation, meningeal involvement was more commonly seen in malignancies such as acute lymphoblastic leukaemia. This problem will now develop in fewer than 5% of patients.5
Intrathecal chemotherapy is the mainstay of treatment, with the suggestion that it may improve patient outcome. There is general presumption that penetration of the CNS is poor with most drugs, with the exception to methotrexate, cytarabine, and thiotepa, which need to be given in high dose to reach therapeutic concentrations.2
On the other hand, some studies showed that systemic methotrexate might be more beneficial than intrathecal administration in specific types of cancer such as breast cancer.8
Other treatment modalities have limited indications, such as surgery for ventriculoperitoneal shunt in patients with symptomatic hydrocephalus or radiotherapy to decrease brain metastasis bulk which limits the chemotherapy penetration.
Median survival is 1.8 months, which potentially could increase to 5.7 months in those patients responding to chemotherapy. Assessment can include change in CSF cytology or clinical improvement.5
- In patients known to have malignancy with signs suggestive of CNS involvement, negative imaging does not exclude serious pathology.
- Malignant meningitis is a more recognisable complication and should still be considered as a “treated” or “non-active” malignancy.