Headache and backache, sometimes with sciatica, are common but not invariable. Polyradiculopathies (particularly of the cauda equina), multiple cranial nerve palsies, and a confusional state have been the principal manifestations, and many cases are restricted to one of these features. Only a small number have an uncomplicated meningeal syndrome of headache, nausea, and meningismus, but these features develop within weeks in many cases. Delirium, stupor, and coma follow. Focal neurologic signs and seizures may be associated, and somewhat fewer than half the patients develop hydrocephalus. The combination of a cranial neuropathy, such as unilateral facial weakness, hearing loss (suggestive of lymphoma), or ocular motor palsy, with bilateral asymmetrical limb weakness is particularly characteristic. The evolution in all these syndromes is generally subacute over weeks with a more rapid phase as the illness progresses.
Neoplastic meningitis presents a characteristic pattern on imaging studies, particularly with gadolinium enhanced MRI of the brain or spine. The leptomeninges are found to be thickened and variably enhancing, sometimes with nodular appearing lesions but as often with smooth contiguous areas of involvement. The basilar portions of the brain, around the cisternal segments of the cranial nerves and overlying the cerebellar folia are preferred regions for appearance of these findings (Fig. 30-11). There may be hydrocephalus but it is surprisingly infrequent.
The diagnosis is established by identifying tumor cells in the CSF using cytology and flow cytometry techniques. We generally undertake an examination of the CSF with the exception of cases with noncommunicating hydrocephalus. In the latter instance, a ventricular drain may have been placed and CSF can be obtained from that source. More than one examination, using generous quantities of CSF, may be needed. Increased pressure in the subarachnoid space, elevation of CSF protein and low glucose levels, and lymphocytic pleocytosis (up to 100 cells but typically much fewer) are other common findings. Nevertheless, in a few patients, the CSF remains persistently normal. Measurement of certain biochemical markers of cancer in the CSF—such as lactate dehydrogenase, β-glucuronidase, β2-microglobulin, and carcinoembryonic antigen (CEA)—offers another means of making the diagnosis and following the response to therapy. These markers are most likely to be abnormal in hematologic malignancies but may also be altered in some cases of intracranial infection and parenchymal metastases (Kaplan et al). In many of the cases of meningeal carcinomatosis, there are also parenchymal brain metastases.
Also known is a rare primary malignant melanoma of the meninges that acts in a similar way to carcinomatous meningitis but has the striking feature of bloody CSF (1,000 to 10,000 red blood cells per mm3). The origin of the neoplasm is from native melanotic cells in the meninges. The prognosis is as bleak as it is for metastatic carcinomatous meningitis as discussed by Liubinas et al.
Treatment and outcome of malignant meningitis
This consists mainly of radiation therapy to the symptomatic areas (cranium, posterior fossa, or spine) followed in selected cases by the intraventricular administration of methotrexate, but these measures rarely stabilize neurologic symptoms for more than a few weeks or months. The methotrexate is typically administered into the lateral ventricle via an Ommaya reservoir (12 mg diluted in preservative-free saline) or into the lumbar subarachnoid space through a lumbar puncture needle. Several regimens have been devised, including daily instillation for 3 to 4 days followed by radiation, or methotrexate doses on days 1, 4, 8, 11, and 15.