Neuroprotective effect of reduced glutathione on cisplatin-based chemotherapy in advanced gastric cancer: a randomized double-blind placebo-controlled trial.

PURPOSE: We performed a randomized double-blind placebo-controlled trial to assess the efficacy of glutathione (GSH) in the prevention of cisplatin (CDDP)-induced neurotoxicity. PATIENTS AND METHODS: Fifty patients with advanced gastric cancer treated with a weekly CDDP-based regimen were included in this study. In patients randomized to receive GSH, GSH was given at a dose of 1.5 g/m2 in 100 mL of normal saline solution over a 15-minute period immediately before CDDP administration, and at a dose of 600 mg by intramuscular injection on days 2 to 5. Normal saline solution was administered to placebo-randomized patients. Clinical neurologic evaluation and electrophysiologic investigations have been performed at baseline and after 9 (CDDP dose, 360 mg/m2) and 15 (CDDP dose, 600 mg/m2) weeks of treatment. RESULTS: At the 9th week, no patients showed clinically evident neuropathy in the GSH arm, whereas 16 patients in the placebo arm did. After the 15th week, four of 24 assessable patients in the GSH arm suffered from neurotoxicity versus 16 of 18 in the placebo arm (P = .0001). In confirmation of this neuroprotective effect, the neurophisiologic investigations, based on the evaluation of the median, ulnar, and sural sensory nerve conduction, showed a statistically significant reduction of these values in the placebo arm but not in the GSH arm, above all considering potential amplitude. In this trial, GSH also reduced hemotransfusion requirements (32 v 62 hemotransfusions) and treatment delay (55 v 94 weeks). The response rate was 76% (20% complete response) in the GSH group and 52% (12% complete response) in the placebo arm, confirming preliminary reports about the lack of reduction in activity of cytotoxic drugs induced by GSH. CONCLUSION: This study provides evidence that GSH is a promising and effective new drug for the prevention of CDDP-induced neuropathy, and that it does not reduce the clinical activity of chemotherapeutic drugs.

Ichthyosis accompanied by neurological symptoms with special reference to epilepsy.

5 patients with ichthyosis had a neurological accompaniment: epilepsy in 4, congenital palpebral ptosis, facial pain and neurosis in 1. In one patient epilepsy was combined with multiple malformations (normal dwarfism, prematurely old face, skeletal abnormalities) and oligophrenia. There was considerable variability genetically: 2 sporadic cases, 1 with X-linked transmission, 1 with autosomal dominant and 1 with apparent autosomal recessive heredity. In one case the co-existence of glucose-6-phosphate dehydrogenase deficiency provided proof of X-linked transmission. Further study of larger case-series is needed for a better definition of the nosographic and genetic aspects of non blastomatous neuroectodermatoses in which ichthyosis figures.

[Neurological complications in drug dependence with special reference to the development of epileptic syndromes]. / Complicanze neurologiche nelle tossicodipendenze, con particolare riguardo all'insorgenza di sindromi epilettiche.

33 drug abusers were examined and all of them were addicts to several drugs and always to heroin. Neurological complications occurred rather frequently. One patient had subarachnoid hemorrhage and angiography showed no arteriovenous malformations nor other pathology. Polyneuropathy has been found in one case. 7 patients (21,2%) developed psychotic episodes. Epileptic attacks were found in 5 cases (15,1%). Latency between the onset of drug-abusing and occurrence of the attacks was found to be at least 1 year in two cases and 3 years in the other three. 4 cases suffered from partial complex seizures with secondary generalization and one patient had generalized tonic-clonic attacks. Fits occurred rarely in all cases; one patient had two episodes of partial status. Further research is required because there are few clinical reports in comparison with the experimental ones.