Faculty Bibliography

We studied the effects of intra-arterial chemotherapy on the visual system of 29 consecutive patients with gliomas. As expected, infra-ophthalmic carotid infusion of cisplatin or carmustine (BCNU) was associated with clinically apparent anterior visual pathway lesions. Electroretinography revealed retinal dysfunction in patients without clinical abnormalities. Supra-ophthalmic carotid infusion of cisplatin or BCNU caused no retinal or optic nerve lesions. Electroretinography was abnormal in only one of these patients. Our results indicated that BCNU and cisplatin cause ischemic damage and are toxic to both retinal and neural tissue in patients with gliomas

Deprenyl, a selective inhibitor of monoamine oxidase, type B, which is free of the 'tyramine effect,' may ameliorate symptom fluctuations in advanced Parkinson's disease (PD). We randomized 96 patients with marked symptom fluctuations at three centers to receive either deprenyl 5 mg b.i.d. or placebo in parallel fashion in addition to a previously optimized levodopa/carbidopa (Sinemet) regimen. Disability was recorded hourly at home by patients 3 days weekly during the 2-week baseline and the 6-week treatment period. Disability during the 'on' state was assessed each week by examination. Mean hourly self-assessment of gait improved in 28 of 50 patients (56%) receiving deprenyl (mean degree of improvement 0.25 points on a 0-2 scale) and in 14 of 46 (30.4%) taking placebo (mean 0.15). Mean hourly overall symptom control improved in 29 (58%) taking deprenyl (mean 0.34) and in 12 (26.1%) taking placebo (mean 0.15) (p less than 0.01 for each parameter). No significant improvement occurred in the objective quality of the 'on' state with deprenyl. Mean daily Sinemet dosage decreases were 17% in the deprenyl group and 7% in the placebo group. Adverse effects included nausea, light-headedness, dyskinesias, and hallucinations, all of which abated after the Sinemet dose was reduced. We conclude that deprenyl is of moderate benefit in a majority of patients with symptom fluctuations complicating PD and is generally well tolerated

We treated five patients with 11 supraophthalmic infusions of BCNU at 200 mg/m2 every 2 months. All three patients with residual tumors showed marked CT response after one infusion. Two patients with bilateral tumors had no response on the contralateral side. All four evaluable cases showed evidence of BCNU neurotoxicity. CT findings superficially resembled tumor recurrence, but white matter changes, nonspecific gyral enhancement, and delayed calcification were more indicative of neurotoxicity. There were no procedure-related complications. One autopsy suggested that direct parenchymal damage might be responsible for delayed neurotoxicity. Supraophthalmic BCNU infusion, at this dosage, is too toxic for cerebral tissue

Five patients with hydrocephalus were studied with carbon-11-2-deoxyglucose or 2-deoxy-2-(18F) fluoro-D-glucose and positron emission tomography both prior to and following ventricular shunting. Four subjects had communicating hydrocephalus; the fifth had aqueductal stenosis, two patients had hydrocephalus for three months or less. The three chronic patients were felt to have hydrocephalus for three years or more. After shunting ventricular size decreased in all patients, and all patients showed clinical improvement. The glucose cerebral metabolic rates increased after shunt in the two subjects with recent onset hydrocephalus but paradoxially decreased in the three chronic patients despite clinical improvement. These findings suggest that the cerebrum was metabolically hyperactive prior to shunt due to an unknown mechanism and presumably in response to the presence of hydrocephalus. A dissociation may also exist in the post-shunt period between cerebral metabolism and cerebral blood flow

Cutaneous hyperpigmentation resembling acanthosis nigricans developed in two patients with malignant brain tumors following chemotherapy with triazinate (Baker's Antifol), a folic acid antagonist. In both cases, the eruption resolved after the cessation of drug administration and reappeared after the reinstitution of triazinate therapy. A skin biopsy specimen from one patient showed microscopic changes consistent with those found in acanthosis nigricans. The other patient had a decreased serum folate level that returned to normal as the hyperpigmentation resolved. Folate may have a role in triazinate-induced acanthosislike hyperpigmentation