INTRATHECAL ACTIVATION OF THE COMPLEMENT-SYSTEM AND DISABILITY IN MULTIPLE-SCLEROSIS

Background: The pathogenesis of multiple sclerosis (MS) appears to inv olve autoimmune phenomena in the central nervous system. Activation of the complement system is suggested to be involved in the pathogenesis . Patients and methods: Cerebrospinal fluid (CSF) and plasma samples f rom 65 patients with acute optic neuritis (ON) as a possible first sym ptom of MS (n=18), ON (n=16) or other attacks of clinically definite M S (n=15), and neurological control subjects (n=16) were studied. Activ ation of the initial part of the complement activation cascade was ass essed by measuring activation of the C3 molecule; terminal activation of the complement cascade was assessed by measuring the terminal compl ement complex (TCC). Demyelination was estimated by the CSF concentrat ion of myelin basic protein and neurological disability was assessed w ith the Kurtzke expanded disability status scale (EDSS) score. Results : Activation of the initial part of the complement activation cascade occurred in each of the three groups of patients with demyelinating di sease, but was not correlated to demyelination or disability. Increase d concentrations of TCC were detected in patients with attacks of MS o ther than ON. The CSF concentrations of TCC, myelin basic protein (MBP ) and neurological disability correlated significantly. The strongest correlation was between neurological disability and the CSF concentrat ion of TCC (r=0.55, P=0.003). Interpretation: Full activation of the c omplement cascade during attacks of MS may be restricted to patients w ith more advanced disease and is significantly correlated to the degre e of neurological disability. This suggests that specific treatment wi th agents that inhibit complement activation may interfere with mechan isms involved in the pathogenesis of neurological disability in patien ts with MS. (C) 1998 Elsevier Science B.V.