title: Clinical and biological changes under treatment with lithium carbonate and valproic acid in sporadic amyotrophic lateral sclerosis.
abstract: The aim of this study was to evaluate the ability of lithium carbonate and valproate cotreatment to modify the survival rate and functional score of patients with definite sporadic amyotrophic lateral sclerosis (ALS). The clinical response of 18 enrolled patients was compared to the evolution of 31 ALS out-patients, carefully paired by age, gender, evolution rate and time of the disease, who never received treatment with lithium and/or valproate. The ALS functional rating scale, revised version (ALSFRS-R), was applied at baseline, 1 month, and every 4 months until the outcome (death or an adverse event). Biochemical markers, such as Cu/Zn superoxide dismutase and glutathione peroxidase activity, and reduced glutathione were assayed in plasma samples obtained at the baseline visit and after 5 and 9 months of treatment. Our results showed that lithium and valproate cotreatment significantly increased survival (p=0.016), and this treatment also exerted neuroprotection in our patients because all three markers reached levels that were not significantly different from the matched samples of healthy donors. The trial stopped after 21 months, when the sample was reduced to under two-thirds, due to the late adverse events of the treatment. The results call for large randomized clinical trials with the dual association, but at low doses to avoid adverse events.
authors.affiliation: Clinical Investigation Laboratory, Instituto Nacional de Neurología y Neurocirugía "Manuel Velasco Suárez", México, D.F., México; Nerve and Muscle Clinic, Instituto Nacional de Neurología y Neurocirugía "Manuel Velasco Suárez", México, D.F., México. Electronic address: bollneur@gmail.com.
authors.forename: Marie-Catherine
authors.initials: MC
authors.lastname: Boll
authors.affiliation: Clinical Investigation Laboratory, Instituto Nacional de Neurología y Neurocirugía "Manuel Velasco Suárez", México, D.F., México. Electronic address: leobayliss@gmail.com.
authors.forename: Leo
authors.initials: L
authors.lastname: Bayliss
authors.affiliation: Nerve and Muscle Clinic, Instituto Nacional de Neurología y Neurocirugía "Manuel Velasco Suárez", México, D.F., México. Electronic address: stevenvc@hotmail.com.
authors.forename: Steven
authors.initials: S
authors.lastname: Vargas-Cañas
authors.affiliation: Department of Neurophysiology, Instituto Nacional de Neurología y Neurocirugía "Manuel Velasco Suárez", México, D.F., México. Electronic address: burgosneurofisio@yahoo.com.mx.
authors.forename: Jorge
authors.initials: J
authors.lastname: Burgos
authors.affiliation: Department of Neurochemistry, Instituto Nacional de Neurología y Neurocirugía "Manuel Velasco Suárez", México, D.F., México. Electronic address: sergiomontes@hotmail.com.
authors.forename: Sergio
authors.initials: S
authors.lastname: Montes
authors.affiliation: Department of Neurochemistry, Instituto Nacional de Neurología y Neurocirugía "Manuel Velasco Suárez", México, D.F., México. Electronic address: dammerung.traume@gmail.com.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Peñaloza-Solano
authors.affiliation: Department of Neurochemistry, Instituto Nacional de Neurología y Neurocirugía "Manuel Velasco Suárez", México, D.F., México. Electronic address: crios@correo.xoc.uam.mx.
authors.forename: Camilo
authors.initials: C
authors.lastname: Rios
authors.affiliation: Department of Neurochemistry, Instituto Nacional de Neurología y Neurocirugía "Manuel Velasco Suárez", México, D.F., México. Electronic address: miyealcaraz@yahoo.com.
authors.forename: Mireya
authors.initials: M
authors.lastname: Alcaraz-Zubeldia
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy* / Q000378:metabolism* / Q000401:mortality; D002104:Cadmium / Q000097:blood / Q000652:urine; D002423:Cause of Death; D004185:Disability Evaluation; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D053208:Kaplan-Meier Estimate; D016651:Lithium Carbonate / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D018709:Statistics, Nonparametric; D013482:Superoxide Dismutase / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D014635:Valproic Acid / Q000627:therapeutic use*
chemical_list: D004791:Enzyme Inhibitors; C000606290:SOD1 protein, human; D002104:Cadmium; D016651:Lithium Carbonate; D014635:Valproic Acid; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D005978:Glutathione
keywords: ALSFRS-R; Amyotrophic lateral sclerosis; Glutathione peroxidase; Lithium carbonate; Superoxide dismutase 1; Valproic acid