Ganglioside GM1 in acute ischemic stroke. The SASS Trial. Effects of GM1 ganglioside in cerebrovascular diseases: a double-blind trial in 40 cases. GM1 ganglioside therapy in acute ischemic stroke. Italian Acute Stroke Study--Hemodilution + Drug. Results of a prospective randomized trial for treatment of severely brain-injured patients with hyperbaric oxygen. Recovery of motor function after spinal-cord injury--a randomized, placebo-controlled trial with GM-1 ganglioside. Trial of ganglioside GM1 in acute stroke. Quality of life and survival in patients with advanced non-small cell lung cancer receiving supportive care plus chemotherapy with carboplatin and etoposide or supportive care only. A multicentre randomised phase III trial. Joint Lung Cancer Study Group. Combined radiotherapy and chemotherapy with dibromodulcitol and CCNU in the postoperative treatment of malignant gliomas. Spinal cord stimulation in the treatment of non-reconstructable stable critical leg ischaemia: results of the European Peripheral Vascular Disease Outcome Study (SCS-EPOS).
We sought to assess the safety and efficacy of ganglioside GM1 in acute (< or = 48 hours), anterior circulation ischemic stroke.
                We screened more than 5000 patients at 13 centers in a randomized, double-blind, placebo-controlled, parallel-treatment, clinical trial and enrolled 287 patients. They received 100 mg GM1 or placebo intramuscularly daily for 28 days and were evaluated regularly for 84 days. Number of deaths, the Toronto Stroke Scale, and the Barthel Index were primary outcomes; improvements on the Fugl-Meyer Scale and on a neuropsychological battery were secondary outcomes.
                The groups were balanced for severity, side of stroke, age, sex, race, years of schooling, prior illness, and depression scores. Analyzable data were available on 275 patients; 217 patients completed the trial. Protocol-specified primary and secondary outcome measures showed no significant difference between treatment arms. However, improvement from baseline in the motor component of the Toronto Stroke Scale favored the GM1-treated group at day 28 when GM1 treatment stopped (P = .020); at day 84, the difference still favored the GM1-treated group (P = .057). All 10 components of the Barthel Index, the Fugl-Meyer Scale, and four of the five tests in the neuropsychological battery also favored the GM1 group. Adverse experiences were similar in the two groups.
                GM1 is safe. However, since only certain post hoc tests showed statistically significant differences or trends favoring GM1, another clinical trial is needed to demonstrate efficacy. A randomized, double-blind trial on the effects of GM1 ganglioside in cerebrovascular diseases was done on 40 patients; the treatment (40 mg/day i.m. injection) began after the acute phase and lasted 6 weeks. 18 cases took the drug and 16 the placebo. The evaluation of the cases was made by graduating the severity of the clinical signs, and some neurophysiological and morphological parameters, i.e., EEGs, flash-evoked potentials and computer tomography scans. We found that the drug, in comparison with the placebo treatment, improved the clinical signs and also the neurophysiological parameters, whereas it was ineffective for the morphological damage. These data seem of some interest in relation to the action of GM1 ganglioside in the processes of neurotransmission and neuronal plasticity as described in the experimental animal. Eleven of 31 clinical centers participating in the Italian Acute Stroke Study--Hemodilution carried out a preliminary study on the effectiveness of ganglioside GM1 in acute stroke; 502 patients were randomized to GM1 (GM1, n = 121), GM1 plus hemodilution (GM1 + H, n = 128), placebo (P, n = 130), or placebo plus hemodilution (P + H, n = 123) groups less than or equal to 12 hours after onset of a hemispheric cerebral infarct. The patients were treated for 15 days and were evaluated on Days 21 and 120 after the onset of stroke. Intention-to-treat analysis failed to show any differences in neurologic deficit, mortality, or neurologic disability among the groups. Efficacy analysis showed a significantly higher degree of neurologic improvement in GM1 group patients compared with patients in the P group during the first 15 days. GM1-treated patients (GM1 and GM1 + H groups) showed a significantly higher degree of neurologic improvement during the first 10 days compared with the placebo-treated patients (P and P + H groups). These differences were no longer statistically significant at Day 120. Our results provide a rationale for the planning of a larger, multicenter trial of GM1 ganglioside in acute stroke. The authors enrolled 168 patients with closed-head trauma into a prospective trial to evaluate the effect of hyperbaric oxygen in the treatment of brain injury. Patients were included if they had a total Glasgow Coma Scale (GCS) score of 9 or less for at least 6 hours. After the GCS score was established and consent obtained, the patient was randomly assigned, stratified by GCS score and age, to either a treatment or a control group. Hyperbaric oxygen was administered to the treatment group in a monoplace chamber every 8 hours for 1 hour at 1.5 atm absolute; this treatment course continued for 2 weeks or until the patient was either brain dead or awake. An average of 21 treatments per patient was given. Outcome was assessed by blinded independent examiners. The entire group of 168 patients was followed for 12 months, with two patients lost to follow-up study. The mortality rate was 17% for the 84 hyperbaric oxygen-treated patients and 32% for the 82 control patients (chi-squared test, 1 df, p = 0.037). Among the 80 patients with an initial GCS score of 4, 5, or 6, the mortality rate was 17% for the hyperbaric oxygen-treated group and 42% for the controls (chi-squared test, 1 df, p = 0.04). Analysis of the 87 patients with peak intracranial pressures (ICP) greater than 20 mm Hg revealed a 21% mortality rate for the hyperbaric oxygen-treated patients, as opposed to 48% for the control group (chi-squared test, 1 df, p = 0.02). Myringotomy to reduce pain during hyperbaric oxygen treatment helped to reduce ICP. Analysis of the outcome of survivors reveals that hyperbaric oxygen treatment did not increase the number of patients in the favorable outcome categories (good recovery and moderate disability). The possibility that a different hyperbaric oxygen treatment paradigm or the addition of other agents, such as a 21-aminosteroid, may improve quality of survival is being explored. Spinal-cord injury is devastating; until recently, there was no medical treatment to improve recovery of the initial neurologic deficit. Studies in animals have shown that monosialotetrahexosylganglioside (GM-1) ganglioside enhances the functional recovery of damaged neurons.
                A prospective, randomized, placebo-controlled, double-blind trial of GM-1 ganglioside was conducted in patients with spinal-cord injuries. Of 37 patients entered into the study, 34 (23 with cervical injuries and 11 with thoracic injuries) completed the test-drug protocol (100 mg of GM-1 sodium salt or placebo intravenously per day for 18 to 32 doses, with the first dose taken within 72 hours of the injury) and a one-year follow-up period. Neurologic recovery was assessed with the Frankel scale (comprising five categories) and the American Spinal Injury Association (ASIA) motor score (a scale of scores from 0 to 100, derived from strength tests of 20 specific muscles, each scored from 0 to 5).
                There was a significant difference between groups in the distribution of improvement of Frankel grades from base line to the one-year follow-up (improvement of 0, 1, 2, and 3 grades in 13, 4, 1, and 0 patients, respectively, in the placebo group and 8, 1, 6, and 1 patients, respectively, in the GM-1 group; P = 0.034 by the Cochran-Mantel-Haenszel chi-square test). The GM-1-treated patients also had a significantly greater mean improvement in ASIA motor score from base line to the one-year follow-up than the placebo-treated patients (36.9 vs. 21.6 points; P = 0.047 by analysis of covariance with the base-line ASIA motor score as the covariate). An analysis of individual muscle recoveries revealed that the increased recovery in the GM-1 group was attributable to initially paralyzed muscles that regained useful motor strength rather than to strengthening of paretic muscles.
                This small study provides evidence that GM-1 enhances the recovery of neurologic function after one year. A larger study must be conducted, however, before GM-1 is considered efficacious and safe in treating spinal-cord injury. Ganglioside GM1 (100 mg) was given daily by intramuscular injection for 28 days in a double-blind placebo controlled trial of acute stroke. No significant difference was detected in a 6 month follow-up period between well matched control and active groups. Although the number of patients studied was small the findings are believed to indicate that GM1 is unlikely to be of value in the treatment of acute stroke in the dose and route of administration used. The aim of the present trial was to evaluate the effects of chemotherapy on the quality of life and survival of patients with advanced non-small cell lung cancer (NSCLC) (stage IIIB or IV). In a controlled multicentre trial, patients were randomised to receive supportive care only or supportive care plus chemotherapy. Chemotherapy consisted of intravenous (i.v.) carboplatin 300 mg/m2 on day 1 and etoposide 120 mg/m2 orally on days 1-5 every 4 weeks for a maximum of eight courses. Quality of life was measured at randomisation and prior to each treatment course and at corresponding 4-week intervals in the control arm, using the EORTC QLQ-C30 + LC13 questionnaire. 48 patients were randomised (supportive care 26, chemotherapy 22), being eligible for comparative analyses. Another 102 patients, 97 of which received chemotherapy, were subsequently included in the study on an individual treatment preference basis. Data from these patients were used for confirmative purposes. Patients in the chemotherapy group reported better overall physical functioning and symptom control compared with the supportive care group. Group differences were smaller within the psychosocial domain, although trends were seen in favour of the chemotherapy group. No significant differences were seen in favour of the supportive care group, except for hair loss. Median survival times were 29 weeks in the chemotherapy group versus 11 weeks in the supportive care group, and 1-year survival rates were 28% versus 8%. Quality of life and survival outcomes were similar in the randomised and non-randomised patients receiving chemotherapy. No treatment-related deaths occurred. In conclusion, treatment with carboplatin and etoposide can improve both the quality of life and the survival of patients with advanced NSCLC. Within 4 weeks after definitive surgery, 91 patients with supratentorial glioblastomas and malignant astrocytomas were randomized to one of three treatment arms: Group 1 received radiotherapy alone; Group 2 received dibromodulcitol (DBD) during radiotherapy, and treatment was then continued with DBD; and Group 3 received DBD during radiotherapy, followed by combination chemotherapy of CCNU and DBD. No severe myelotoxicity occurred, but combined treatment with CCNU and DBD occasionally caused a transient myelosuppression. Statistical analysis of 84 evaluable patients showed a significantly longer survival period in those who received chemotherapy during and after irradiation. Median survival times in the three groups were 40, 57, and 60 weeks, respectively; the corresponding p value for Groups 2 and 3 was 0.025 and 0.0015. The ratio of patients surviving over 18 and 24 months was highest in Group 3. This study suggests that the administration of DBD during irradiation might have been the main factor in improving survival times. To determine the effect of spinal cord stimulation (SCS) on limb survival in patients with non-reconstructable critical leg ischaemia, and the value of patient selection on the basis of transcutaneous oxygen pressure (TcpO2) measurements and trial screening.
                A prospective, controlled, European multicentre study.
                Non-reconstructable patients with stable critical leg ischaemia were divided into three groups. The SCS-Match group comprised patients with a baseline forefoot TcpO2 of < 30 mmHg and both sufficient pain relief and sufficient paraesthesia coverage (> 75%) after a test stimulation period of at least 72 h. If baseline TcpO2 was < 10 mmHg, the TcpO2 should have exceeded 20 mmHg after test stimulation. The SCS-Match group was compared with patients not meeting these criteria, who were treated either with SCS (SCS-No-Match) or without SCS (No-SCS).
                At baseline, the mean (+/- SD) supine TcpO2 was 14.9 +/- 8.3 mmHg in the SCS-Match group (n = 41), 11.3 +/- 13.3 mmHg in the SCS-No-Match group (n = 32) and 15.3 +/- 17.1 mmHg in the No-SCS group (n = 39). In the SCS-Match group a significant improvement in pain relief (p < 0.005) and TcpO2 (p < 0.001) was seen. After 12 months, cumulative limb survival of patients treated with SCS was significantly better than that of patients not treated with SCS (p < 0.03), and limb survival in the SCS-Match group was significantly higher (p < 0.03) than that in the SCS-No-Match and No-SCS groups (78, 55 and 45%, respectively).
                SCS treatment of non-reconstructable critical leg ischaemia provides a significantly better limb survival rate compared with conservative treatment. Patient selection based on TcpO2 and the results of trial screening further increase the probability of limb survival after SCS therapy.
The evidence available does not support the use of ganglioside treatment to reduce the death rate in SCI patients. No evidence has yet emerged that ganglioside treatment improves recovery or quality of life in survivors.