Search

Objective: To evaluate Bacille Calmette-Guérin (BCG) effects after clinically isolated syndromes (CIS). Methods: In a double-blind, placebo-controlled trial, participants were randomly assigned to receive BCG or placebo and monitored monthly with brain MRI (6 scans). Both groups then entered a preplanned phase with IM interferon-?-1a for 12 months. From month 18 onward, the patients took the disease-modifying therapies (DMTs) that their neurologist considered indicated in an open-label extension phase lasting up to 60 months. Results: Of 82 randomized subjects, 73 completed the study (33 vaccinated and 40 placebo). During the initial 6 months, the number of cumulative lesions was significantly lower in vaccinated people. The relative risks were 0.541 (95% confidence interval [CI] 0.308-0.956; p = 0.03) for gadolinium-enhancing lesions (the primary endpoint), 0.364 (95% CI 0.207-0.639; p = 0.001) for new and enlarging T2-hyperintense lesions, and 0.149 (95%CI 0.046-0.416; p = 0.001) for new T1-hypointense lesions. The number of total T1-hypointense lesions was lower in the BCG group at months 6, 12, and 18: mean changes from baseline were - 0.09 ± 0.72 vs 0.75 ± 1.81 (p = 0.01), 0.0 ± 0.83 vs 0.88 ± 2.21 (p = 0.08), and -0.21 ± 1.03 vs 1.00 ± 2.49 (p = 0.02). After 60 months, the cumulative probability of clinically definite multiple sclerosis was lower in the BCG 1 DMT arm (hazard ratio = 0.52, 95% CI 0.27-0.99; p < 0.05), and more vaccinated people remained DMT-free (odds ratio = 0.20, 95% CI 0.04-0.93; p = 0.04). Conclusions: Early BCG may benefit CIS and affect its long-term course. Classification of evidence: BCG, as compared to placebo, was associated with significantly reduced development of gadolinium-enhancing lesions in people with CIS for a 6-month period before starting immunomodulating therapy (Class I evidence). © 2013 American Academy of Neurology.

Objective: Aim of our study was to determine if lithium was safe and well tolerated in MSA patients. Secondary objectives were the effect of lithium on disease progression, quality of life, and depression. Background Multiple system atrophy (MSA) is a rare, sporadic, progressive neurodegenerative disease. Oligodendrocyte cytoplasmic inclusions of fibrillized alpha-synuclein represent the hallmark of the disease. It was demonstrated that lithium is able to stimulate autophagy, and to efficiently remove protein aggregates, including alpha-synuclein. Design/Methods: We designed a double-blind, placebo-controlled, randomized pilot clinical trial to test the safety and tolerability of 48 weeks of treatment with lithium in MSA. Lithium was administered starting from 150 mg twice-daily. The dose was increased of 300 mg at each visit until lithium serum levels reached 0.9-1.2 mMol/L. The maximum allowed dose was 1500 mg/day. Results: Ten patients were enrolled after informed consent was obtained. Nine patients were randomized, four received lithium and five placebo. In the lithium group one patient died, and the other three abandoned the trial for side effects. Two patients reached the target serum levels of lithium, the other two patients stopped at 0.8, and 0.5 mMol/L when AEs forced them to abandon the trial. One patient of the placebo group died. No other patient retired in the placebo group. An interim analysis was performed one year after the first patient was randomized. The results showed a proportion of trial abandon/death of 100% in the lithium and 20% in the placebo group (p Conclusions: Lithium was overall not well tolerated and caused all of the treated patients to abandon the trial. No conclusions can be drawn on the effects of lithium on secondary endpoints of the study. We do not encourage future studies with lithium in MSA patients. Supported by: “Associazione Italiana per la lotta alle Sindromi Atassiche (AISA) sez. Campania”. Disclosure: Dr. Sacca has nothing to disclose. Dr. Marsili has nothing to disclose. Dr. Brunetti has nothing to disclose. Dr. Carbone has nothing to disclose. Dr. De Michele has nothing to disclose. Dr. Pane has nothing to disclose. Dr. Russo has nothing to disclose. Dr. Salvatore has nothing to disclose. Dr. Tucci has nothing to disclose. Dr. Quarantelli has nothing to disclose. Dr. Filla has nothing to disclose.