title: Relationship of CSF neurotransmitter metabolite levels to disease severity and disability in multiple sclerosis.
abstract: Axonal degeneration and brain tissue loss occur during disease progression in multiple sclerosis (MS) and are expected to influence neurotransmitter activities, with consequences on neurologic and psychiatric symptomatology. We searched for relationships of disease duration, disability, and severity of MS patients to CSF levels of the major metabolites of noradrenaline, dopamine, and serotonin, MHPG, methoxyhydroxyphenylglycol (MHPG), homovanillic acid, and 5-hydroxyindoleacetic acid (5-HIAA), respectively, in 39 patients with relapsing-remitting (RR) MS in remission, and 26 patients with progressive (PR) MS. Disability and Disease Severity were assessed by the Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Severity Score (MSSS). Compared with the levels of 50 control subjects, MHPG levels were not different in either MS group, correlated negatively to duration of illness and number of relapses in the RRMS group, but not to EDSS score or to MSSS. Homovanillic acid levels were significantly lower only in the PRMS group, with a negative correlation to duration of illness, and a strong negative correlation to EDSS score, but not to MSSS. 5-HIAA was significantly lower in both RRMS and PRMS groups. In the RRMS group, 5-HIAA levels were negatively related to EDSS and to MSSS. Multiple regression analyses revealed a significant association of MHPG to duration of illness, and a strong negative association of 5-HIAA to MSSS rather than to EDSS. The strong negative correlation of MSSS to CSF 5-HIAA levels in RRMS group of patients indicates that deficits in central serotonergic activity are related to the rate of disability accumulation in RRMS, and could be linked to the reported reduction of disease activity by serotonergic drugs.
authors.affiliation: Department of Neurology, Athens University Medical School, Eginition Hospital, Athens, Greece. markian@otenet.gr
authors.forename: Manolis
authors.initials: M
authors.lastname: Markianos
authors.forename: Georgios
authors.initials: G
authors.lastname: Koutsis
authors.forename: Maria-Eleftheria
authors.initials: ME
authors.lastname: Evangelopoulos
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Mandellos
authors.forename: Georgios
authors.initials: G
authors.lastname: Karahalios
authors.forename: Constantin
authors.initials: C
authors.lastname: Sfagos
mesh_terms: D000293:Adolescent; D000328:Adult; D004185:Disability Evaluation; D018450:Disease Progression; D005260:Female; D006719:Homovanillic Acid / Q000134:cerebrospinal fluid*; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid*; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000134:cerebrospinal fluid*; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid* / Q000503:physiopathology*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D012044:Regression Analysis; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D018377:Neurotransmitter Agents; D008734:Methoxyhydroxyphenylglycol; D006897:Hydroxyindoleacetic Acid; D006719:Homovanillic Acid