Neurology, Neurologie, Sciences biologiques et medicales, Biological and medical sciences, Sciences medicales, Medical sciences, Neurologie, Neurology, Sclérose en plaques et variantes. Syndrome de guillain barré et autres polyradiculonévrites inflammatoires. Leucoencéphalites, Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis, Enzymopathie, Enzymopathy, Enzimopatía, Maladie héréditaire, Genetic disease, Enfermedad hereditaria, Maladie inflammatoire, Inflammatory disease, Enfermedad inflamatoria, Maladie métabolique, Metabolic diseases, Metabolismo patología, Pathologie du système nerveux central, Central nervous system disease, Sistema nervosio central patología, Acide lactique, Lactic acid, Láctico ácido, Cytopathie mitochondriale, Mitochondrial disorder, Citopatía mitocondrial, Dégénérescence, Degeneration, Degeneración, Glucose, Glucosa, Lactate, Lactates, Lactato, Liquide céphalorachidien, Cerebrospinal fluid, Líquido cefalorraquídeo, Mitochondrie, Mitochondria, Mitocondria, Métabolisme, Metabolism, Metabolismo, Pathologie du système nerveux, Nervous system diseases, Sistema nervioso patología, Sclérose en plaques, Multiple sclerosis, Esclerosis en placa, Trouble fonctionnel, Dysfunction, Trastorno funcional, Energy, Mitochondrial, Polyol, and Progression
In contrast to relapse, the mechanisms of multiple sclerosis (MS) disease progression are less understood and appear not to be exclusively inflammatory in nature. In this pilot study we investigated the relationship between disturbed CNS energy metabolism and MS disease progression. We tested the hypothesis that cerebrospinal fluid (CSF) concentrations of sorbitol, fructose, and lactate, all metabolites of extra-mitochondrial glucose metabolism, would be elevated in secondary progressive (SP) MS patients and would be associated with worsening neurologic disability. We measured metabolite concentrations by gas chromatographic/mass spectrometric and enzymatic methods in archived CSF samples from 85 MS patients [31 relapsing-remitting (RR) and 54 SP patients( and 18 healthy controls. We found that concentrations of all three metabolites, but not concentrations of glucose or myoinositol, were significantly increased in CSF from SP and, to a lesser degree, RR patients, compared to controls. Furthermore, CSF concentrations of sorbitol and fructose (polyol pathway metabolites), but not lactate (anaerobic glycolysis metabolite), correlated positively and significantly with Expanded Disability Status Scale (EDSS) score, an index of neurologic disability in MS patients. We conclude that extra-mitochondrial glucose metabolism is increased in MS patients and is associated with disease progression evidenced by increasing EDSS score. As extra-mitochondrial glucose metabolism increases with impaired mitochondrial metabolism of glucose, these findings implicate mitochondrial dysfunction in the pathogenesis of MS disease progression. CSF metabolic profiling may be useful in clarifying the role of mitochondrial pathology in progression and in targeting and monitoring therapies for disease progression that aim to preserve or boost mitochondrial glucose metabolism.