title: Heightened intrathecal release of axonal cytoskeletal proteins in multiple sclerosis is associated with progressive disease and clinical disability.
abstract: The pathologic basis of disease progression in multiple sclerosis (MS) is thought to involve axonal degeneration, which contributes to the accumulation of neurological disability. Recent reports suggest that intrathecal concentrations of the neurofilament protein in relapsing remitting MS correlate with disease activity and the degree of disability. We sought to investigate the intrathecal levels of other cytoskeletal components of axons, primarily actin, tubulin and the light subunit of neurofilament (NFL) in patients with progressive MS and relevant controls and correlate results with clinical parameters of disease severity. Cerebrospinal fluid (CSF) concentrations of actin, tubulin and NFL were significantly increased in MS patients when compared to corresponding levels in patients with other inflammatory or non-inflammatory neurological diseases. Moreover, the intrathecal release of actin and tubulin, and to a lesser extent NFL, was significantly more marked in patients with primary and secondary progressive MS when compared to patients with relapsing remitting disease and was correlated with clinical disability. Our findings suggest that progressive MS is associated with the heightened intrathecal release of axonal cytoskeletal proteins, and that CSF actin, tubulin and NFL are reliable markers of axonal damage.
authors.affiliation: Department of Neuroimmunology, Guy's, King's and St. Thomas' School of Medicine, Guy's Hospital, SE1 9RT, England, London, UK.
authors.forename: Y K
authors.initials: YK
authors.lastname: Semra
authors.forename: O A
authors.initials: OA
authors.lastname: Seidi
authors.forename: M K
authors.initials: MK
authors.lastname: Sharief
mesh_terms: D000199:Actins / Q000134:cerebrospinal fluid*; D001369:Axons / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism; D004185:Disability Evaluation; D018450:Disease Progression; D006801:Humans; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid*; D016900:Neurofilament Proteins / Q000134:cerebrospinal fluid*; D011237:Predictive Value of Tests; D014404:Tubulin / Q000134:cerebrospinal fluid*
chemical_list: D000199:Actins; D016900:Neurofilament Proteins; D014404:Tubulin