Leukoencephalopathy following the administration of methotrexate into the cerebrospinal fluid in the treatment of primary brain tumors

Abstract

Four children having recurrent primary malignant posterior fossa tumors de‐developed a leukoencephalopathy during treatment with methotrexate administered via a ventriculocisternal catheter. Symptoms and signs, including visual disturbances; seizures, quadriparesis, and organic dementia appeared from 3 to 15 months following the initiation of methotrexate therapy. At autopsy all four patients had severe leukoencephalopathy, chiefly involving die central white matter of the cerebral hemispheres; one patient had no residual tumor. All patients had received earlier irradiation, but the lesions within the brain are believed not to represent irradiation necrosis. It is postulated that the changes occurring within the brain are secondary to the disturbances in brain folic acid metabolism produced by the methotrexate; this effect may have been accentuated by the blockage of the cerebrospinal fluid pathways, the delayed effects of irradiation, or the administration of anticonvulsants. Intrathecal methotrexate is capable of eradicating certain intracranial malignancies, but its administration must be more judicious in order to avoid lethal complications.

Intracerebral (parenchymal) infusion of methotrexate: report of a case

“…A chemical arachnoiditis is the most common form of acute toxicity seen following intrathecal MTX [1]. The pathological sequelae in both acute and delayed reactions most consistently include some form of leukoencephalopathy [3,4,13,14]. Periventricular lesions are characteristic following intrathecal administration of MTX [3,4,13].…”

“…The pathological sequelae in both acute and delayed reactions most consistently include some form of leukoencephalopathy [3,4,13,14]. Periventricular lesions are characteristic following intrathecal administration of MTX [3,4,13]. Prolonged ependymal exposure causes disruption of the intact ventricular barrier, thus promoting transependymal diffusion of the drug and accounting for the periventricular distribution of some lesions [3,13,15,16].…”

Intrathecal Administration of Y-27632, a Specific Rho-Associated Kinase Inhibitor, for Rat Neoplastic Meningitis

“…The intrathecal administration of these anticancer agents achieves a therapeutic efficacy of 40% to 70%, and leads to temporary cancer regression for a short period in some cases, but, in other many cases, fails to improve the patient's performance status. Acute neurotoxicity and retarded necrotizing encephalopathy, prevalent adverse effects of methotrexate, impose limitations on the use of doses necessary for satisfactory therapeutic effects (6,7). In addition, patients cannot return to a satisfactory performance status even if intrathecal chemotherapy with these anticancer drugs is able to exert expected biological effects because cancer cells invade the brain, damaging normal brain function.…”

Leukoencephalopathy complicating intraventricular Catheters: clinical, radiographic and pathologic study of 10 cases

“…Although generally safe [31, there are several reports of complications associated with the Ommaya device, primarily meningitis and focal or diffuse necrotizing leukoencephalopathy after inj ecfion of potentially neurotoxic agents [4][5][6][7][8][9]. We have encountered 10 patients with implanted Ommaya devices who developed pericatheter white matter (WM) lesions apparent as focal lucent areas on computed tomographic scan (CT), sometimes with contrast enhancement and/or mass effect.…”