Charles B. Wilson

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

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.

Brain tumor chemotherapy with intrathecal methotrexate

Two patients harboring recurrent posterior fossa tumors were treated with intrathecal methotrexate. The patient with an ependymoma responded dramatically and, when he died of a leukoencephalopathy 2 years later, no evidence of intracranial tumor remained. A medulloblastoma in the second patient responded to methotrexate but became moderately drug resistant and spread to bone. In this case, concomitant use of intrathecal methotrexate and systemic citrovorum factor offered no apparent advantage. Relevant literature relating to methotrexate and tumor kinetics is reviewed. In the light of present knowledge, brain tumors selected for intrathecal methotrexate should be treated weekly for an indefinite period of time. The need for additional information regarding the behavior of citrovorum factor in the central nervous system is acknowledged.

Prolactin-Secreting Tumors in Men: Surgical Cure

Two men presented with decreasing libido and impotence. Endocrine evaluation showed that they both had low levels of serum testosterone and a prolactin-secreting adenoma. Transsphenoidal removal of their tumors resulted in normalization of serum prolactin and testosterone concentrations and normalization of sexual function. These patients represent the first two nonacromegalic men with prolactin-secreting tumors and hypogonadism in whom surgical resection of their tumors resulted in a complete clinical and biochemical remission. We discuss the effects of elevated prolactin on male sexual function.

Acromegaly: Treatment by Cryoablation

Abstract Results of cryoablation of pituitary adenomas in seven patients with acromegaly are described. Objective and subjective improvement, as well as reduction in human growth hormone (HGH) leve...

POLYACRYLAMIDE ELECTROPHORESIS AND IMMUNODIFFUSION STUDIES OF BRAIN TUMOR PROTEINS

One reason for studying the proteins of brain tumors derived from different cell types is the possibility that chemical phenotypes characteristic of a particular tumor type might be established. In vitro studies clearly indicate that cellular morphology is affected by the growth environment, and morphological phenotypes may be difficult to determine in cell culture. An easily identifiable and consistently expressed phenotypic character would be important not only for relating the tumor cell to its normal parent, but also for relating the tumor cell to tissue-cultured and heterotransplan ted cells. Fractionation of soluble proteins from normal human brain has been carried out by electrophoresis on paper (Cumings, 1953) ; Robertson, 1960), starch gel (Cumings, 196 1 ) , agar gel (Karcher et al., 1959; Allegranza & Marobbio, 1962), and polyacrylamide gel (Monseu & Cumings, 1965). Brain-specific proteins have been described by Dencker and co-workers (1960-1962) and Hass ( 1966). This protein was shown to have a mobility in the ap range on immunoelectrophoresis. Warecka and Bauer (1967) demonstrated that this a2-globulin was a glycoprotein, since it could be partially hydrolyzed by neuraminidase and could be stained with periodic acid-Schiff reagent. MacPherson and Liakopoulou ( 1966) also found brain-specific antigens having a az or PI mobility on immunoelectrophoresis. In addition, they described an antigen in rat brain which was species as well as organ specific. Using starch gel electrophoresis, Moore (1965) isolated an acidic, rapidly migrating protein specific to the nervous system and present in the brains of all species examined, including human. Several workers have found the brain-specific a2-globulin in brain tumor tissue and occasionally in cerebrospinal fluid of patients with brain tumors (Dencker et al., 1960-1962; German et al., 1964; Hass, 1966). The purpose of this study was to obtain protein fractions separated by polyacrylamide gel electrophoresis from extracts of human brain tumor specimens. These were compared to the protein fractions from normal temporal lobe cortex and blood serum to determine the presence of unusual proteins in the tumor or the conspicuous absence from the tumor of protein fractions found in normal brain. Immunodiffusion studies were also carried out for the purpose of demonstrating the presence or absence of Moore’s ( 1965) brain-specific S-100 protein.