Brain lesions following combined treatment with methotrexate and craniospinal irradiation

Abstract

Eight patients with meningeal seeding by carcinoma or lymphomas were treated with intravenous (i.v.) and/or intrathecal (i.th.) Methotrexate (MTX). Seven patients received additional craniospinal irradiation and in all seven a fatal encephalopathy developed. On the bases of clinical and morphological findings we identified an acute and a delayed form of encephalopathy and concluded that the concurrent administration of Methotrexate and of craniospinal irradiation increases considerably the risk of brain damage.

Methotrexate‐related leukoencephalopathy without radiation therapy: Distribution of brain lesions and pathological heterogeneity on two autopsy cases

“…The mechanisms of chemotherapy‐induced leukoencephalopathy are also enigmatic. Leukoencephalopathy is particularly common in regimens that include MTX, although other drugs, such as carmustine, melphalan, fludarabine, 5‐FU, and cisplatin have also been implicated 3,6,11,12,14 . In some cases, the pathology appears to be partially or entirely reversible, whereas others show permanent deficits or fatal progression.…”

“…However, this form of therapy is frequently associated with neurologic complications. Generally, a combination of both intrathecal MTX injection and whole brain irradiation is the standard treatment for meningeal carcinomatosis and acute leukemia involving the CNS 1–10 …”

“…To date, there are a few reports describing leukoencephalopathy associated with intrathecal MTX instillation without irradiation 3,6,9,20–24 . Moreover, only two of them had pathological descriptions 3,23 .…”

“…Generally, a combination of both intrathecal MTX injection and whole brain irradiation is the standard treatment for meningeal carcinomatosis and acute leukemia involving the CNS. [1][2][3][4][5][6][7][8][9][10] In 1975, Rubinstein et al coined a new term, disseminated necrotizing leukoencephalopathy (DNL), for the severe, typically progressive and fatal form of the neurological disease induced by intrathecal MTX injection therapy and irradiation. They originally described the disease in children with CNS involvement of acute lymphoblastic leukemia treated with intrathecal chemotherapy of MTX and whole brain irradiation.…”

Primary central nervous system lymphoma

“…Leucovorin is often provided after intrathecal methotrexate to prevent any potential myelosuppression or renal side effects. Concurrent administration of intrathecal methotrexate during whole brain radiotherapy has been associated with a higher risk of disseminated necrotizing leukoencephalopathy [36,Class III]. Radiation therapy preceding intrathecal chemotherapy is associated with an increased incidence of leukoencephalopathy.…”