Neuroelectric blocking factors in human and animal sera evaluated using the isolated frog spinal cord.

Abstract

s The effects of sera from guinea-pigs with experimental allergic encephalomyelitis (EAE) and multiple sclerosis (MS) patients were evaluated and compared with the activity of control sera using the isolated frog spinal cord. Ventral root responses (VRR) were recorded during supramaximal ipsilateral dorsal root stimulation in the presence and absence of 25% serum. In control experiments with normal human and guinea-pig sera we observed a consistent, reversible increase in VRR averaging 20% and 17% respectively, and in no case was any significant decrease produced. In contrast, sera from EAE guinea-pigs 12 to 19 days after injection produced an equally rapid, reversible decrease in VRR. The decrease averaged 36% and was highly significant (P<0.0001) relative to controls. Similarly, sera from MS patients on the average decreased the VRR by 26%, and this again was significant compared with controls (P<10-6).

The pathophysiology of multiple sclerosis⋮ the mechanisms underlying the production of symptoms and the natural history of the disease

“…The suspicion that such factors may exist originated with a study showing that sera from animals with experimental autoimmune encephalomyelitis or from MS patients during acute exacerbation, blocked re£ex activity in cultured central nervous system (CNS) tissue within minutes of exposure and in a complement-dependent manner (Bornstein & Crain 1965). The study was quite small and included few controls, but it was followed by a series of studies which reached similar conclusions (Cerf & Carels 1966;Carels & Cerf 1969;Lumsden et al 1975a,b;Schauf et al 1976 and some others which threw doubt on the interpretation of the data (Crain et al 1975;Seil et al 1975Seil et al , 1976, claiming that the blocking activity was not speci¢c to MS. Where present, the conduction block appears to be contained within the IgG-containing fraction of serum (Crain et al 1975; and it is diminished by plasma exchange Stefoski et al 1982). However, if antibodies are involved, they probably act by means other than demyelination, since the blocking activity is both prompt and reversible.…”

Monoclonal antibody treatment exposes three mechanisms underlying the clinical course of multiple sclerosis

“…4 The effect is reminiscent of the augmentation of symptoms dependent on impaired conduction through demyelinated pathways with local changes in temperature and calcium ion concentration. 13,14 The mediator for this first dose effect is unidentified; we have excluded free TNF-␣ although it remains possible that membrane bound TNF-␣ is inadequately neutralized by soluble TNF-␣ receptor. Experimental studies implicate nitric oxide 15 as a potential cause.…”