Involvement of the cranial nerves or an encephalopathy caused by widespread infiltration of the cranial meninges has been treated with whole-brain radiation, 3,000 cGy, given in fractions of 300 cGy per day for 10 days. Spinal root infiltration responds to spinal radiation, and regional treatments are helpful temporarily for local seeding of the lumbar roots. A study of CSF flow by the injection of a radionuclide agent may be useful to determine if there is impeded flow that prevents circulation of the methotrexate or exposes one region to excessive toxicity. In tumors that are sensitive to a specific chemotherapy, systemic administration may be effective depending on the permeability of the blood–brain barrier to these agents, for example, in some forms of breast cancer, and the systemic use of check point (cell-cycle, e.g., PD-1) inhibitors is being investigated.
The median duration of survival after diagnosis of meningeal carcinomatosis was 6 months in the large series reported by Wasserstrom and colleagues, but only 43 days in the series of Sorenson and coworkers. We have experience, however, with individuals who have survived with stable deficits for over a year with breast cancer metastatic to the meninges and lumbar roots. An encephalopathy caused by widespread tumor infiltration or hydrocephalus is a highly concerning and usually preterminal sign.
The leukoencephalopathy that follows the combined use of intrathecal methotrexate and radiation therapy is described later. Some patients do not survive long enough for the problem to be manifest. The best response to treatment occurs in patients with lymphoma and breast and small cell lung cancers; cases of meningeal infiltration by other lung cancers, melanoma, and adenocarcinoma do less well.
Involvement of the Nervous System in Leukemia
Almost one-third of all leukemic patients, especially with childhood leukemia, have evidence of diffuse infiltration of the leptomeninges and cranial and spinal nerve roots at autopsy (Barcos et al). The incidence is greater in acute than in chronic leukemia and greater in lymphocytic than in myelocytic leukemia; it is also as mentioned far more frequent in children than in adults. The highest incidence is in children with acute lymphocytic (lymphoblastic) leukemia who relapse after treatment with combination chemotherapy (60 to 70 percent at time of death). In those cases, the disease in the meninges may be fulminant. The clinical and CSF picture of meningeal leukemia has many similarities to that of meningeal carcinomatosis discussed earlier, with the qualification that leukemic cells are more likely to be found by cytologic examination of the spinal fluid. The treatment of the two disorders is also similar.
The studies of Price and Johnson demonstrated that CNS leukemia is primarily a pial disease. The earliest evidence of leukemia is detected in the walls of pial veins, with or without cells lying freely in the CSF. The leukemic infiltrate in our pathologic material has extended to the deep perivascular spaces, where the pial-glial membrane often confines it; at this stage the CSF consistently contains leukemic cells. Depending on the severity of meningeal involvement, transgression of the pial-glial membrane eventually occurs, with varying degrees of superficial parenchymal infiltration by collections of leukemic cells. Hemorrhages of varying sizes are another common complication and are sometimes lethal. Chloroma, a solid green-colored mass of myelogenous leukemic cells, may infiltrate the dura or, less often, the brain, but it is distinctly uncommon.