Aclu zyxwvutsrqponmlkjihgfe Neurol Scund 1995: 91: 58-61 Printed in Belgium zyxwvutsrqponm - ull rights reserved Copyright zyxw 0 Munkguard 1995 zyx ACTA NEUROLOGICA SCANDINAVICA ISSN 0001-6314 Increased CSF C4d i neuropathy ind .icates involvement nd the emyelinat radicular Koguchi zyxwvutsrqp Y, Yamada T, Kuwabara S, Nakajima M, Hirayama K. Increased CSF C4d in demyelinating neuropathy indicates the radicular involvement. Acta Neurol Scand 1995: 91: 58-61. zyxwvut 0 Munksgaard 1995. Plasma and cerebrospinal fluid (CSF) levels of C4d and the circulating immune complex (CIC) to Clq were measured in 12 patients with chronic inflammatory demyelinating polyneuropathy and Guillain-Barrk syndrome. CSF C4d values more than 2 SD from the mean of 8 cervical spongylosis cases were demonstrated in the patients with proximal demyelination. The CSF C4d probably originated from both intrathecal synthesis and the systemic circulation. C S F levels of C4d may serve as a sensitive indicator for the radicular involvement in demyelinating polyneuropathy. :hronic inflammatory demyelinating polyneuropa- thy (CIDP) and Guillain-BarrC syndrome (GBS) are thought to be characterized by immune mediated demyelination. Although a role for the cellular and humoral immune system in the initiation of myelin breakdown has not been defined, evidence suggests that complement proteins are involved in both dis- eases. Thus, there are reports of C3 and C9 deposits in peripheral nerves (1,2), elevated C3a and C5a in CSF (3) and detection of soluble C5b-9 (SC5b-9) in CSF (4) and serum (2). zyxwvut In vitro studies indicate that central and peripheral myelin may both be capable of activating the clas- sical zyxwvutsrqp (5) or alternative (6) complement pathway in an antibody-independent manner. In the classical path- way, which may be activated not only by IgG or IgM antibodies, but also by other factors such as trypsin- like enzymes, a virus and myelin, C1 initially binds to the activation site through Clq. C l r activates C l s which cleaves C4 into C4b. C4b, which contains the C4d fragment, then binds covalently to tissue near the site of the initial complement activation. We have reported immunohistochemistry show- ing the frequent appearance of C4d positive struc- tures in various brain areas in progressive supranu- clear palsy and amyotrophic lateral sclerosis; their appearance corresponds to the increased concentra- tion of this protein in the cerebrospinal fluid (CSF) (798). ing Y. Koguchi, T. Yamada, S. Kuwabara, M. Nakajima, K. Hirayama Department of Neurology, School of Medicine, Chiba University, Japan Key words: chronic idiopathic demyelinating; neuropathy; Guillain-Barre syndrome; complement protein; C4d; cerebrospinal fluid Tatsuo Yamada, Chiba University School of Medicine, Dept. of Neurology, 1-8- 1, Inohana, Chuo-ku, Chiba. 260, Japan Accepted for publication April 19, 1994 Here we measured the CSF and plasma concen- trations of C4d, as well as the circulating immune complex to Clq (CIC to Clq), in patients with CIDP and GBS. We found a correlation between increased levels of CSF C4d and neurophysiological data suggesting proximal involvement of peripheral nerves. Material and methods Subjects Seven CIDP (mean age, 48.0 k 16.8) and 5 GBS (mean age, 40.2 & 6.7) were examined in this study. To compare with another disease having a non- immune mediated pathology, we used the data from age-matched (one way ANOVA) 8 cervical spongy- losis (CS) cases (mean age, 41.0 * 10.3). The diag- nosis of CIDP was based on the criteria from the adhoc subcommittee of the American Academy of Neurology (9), with all patients showing definite CIDP in clinical, electrodiagnostic, pathological and CSF studies. The diagnostic criteria of Asbury (10) were used for GBS. Data on the distribution of ages, sexes and disease orientation for each group are given in Table 1. In Case 8, elevation of CSF pro- tein (350 mg/dl) was seen 3 weeks after the onset of GB S but no such elevation was seen at the time used in this study. Case 9 showed poor recovery and did not have Campylobacter jejuni enteritis. zy 58