Studies on the conduction of demyelinated peripheral nerves of the guinea-pig

Experimental allergic neuritis was produced in 77 out of 93 guinea-pigs injected intradermally with antigenic emulsion containing human sciatic nerve and modified Freund's adjuvant. Neurological features of the disease began approximately 17 days following the injection and these were characterised by instability of posture following displacement, symmetrical ataxia of gait and some weakness, especially of the hind limbs. Weight loss usually accompanied the onset of the clinical features in severe cases and only in these animals was any constitutional upset evident. Animals were graded according to their most severe clinical disability. Specimens of sciatic nerve, spinal roots and ganglia as well as parts of the spinal cord were examined histologically. The most striking abnormalities in specimens from diseased animals were found in the sciatic nerve trunk. These consisted of focal areas of demyelination of varying severity with relative sparing of axons. Cellular infiltration with large and small mononuclear cells accompanied the demyelination but this was not an invariable feature. Spinal roots sometimes showed lesions, while lesions in the root ganglia were rare. Sections of spinal cord and other parts of the central nervous system were normal. The possible immunological mechanism in the pathogenesis of the disease is discussed. Electrophysiological observations were made in vitro on whole sciatic nerves and in vivo on spinal roots supplying the medial gastrocnemius muscle. In addition, single afferent fibres from t his muscle were isolated by systematic dissection of dorsal root filaments, identified as coming from muscle stretch receptors and differentiated into muscle spindle and Golgi tendon organ afferents by physiological methods. In all cases, observations were made on normal control animals and the results compared with similar observations on demyelinated nerves from animals with clinical features of experimental allergic neuritis. In the demyelinated nerves, experiments showed that conduction in some fibres was blocked, others continued to conduct, but at reduced velocity and finally some fibres appeared to conduct normally. The possible reasons for these changes in conduction are considered in relation to the normal mechanism of nerve impulse transmission. A comparison is made between the clinical features, conduction velocities and histological changes in guinea-pigs with experimental allergic neuritis and it is concluded that, in general, correlation is best in severely affected animals. In the absence of pathological changes in the central nervous system, neurological features of diseased animals have been explained, on the basis of the defective conduction in the peripheral nerves. Evidence is presented that some animals which made a complete clinical recovery from the disease still had demonstrable lesions in the peripheral nerves associated with defective conduction. An analogy is made between this finding and those found in apparently recovered cases of polyneuritis in humans. Maximum conduction velocity of the nerve to the medial head of gastrocnemius is related to the size of the largest fibres in the same nerve, measured from histological sections. The result is contrasted with results from similar studies by other authors and it is suggested that the myelinated nerves of the cat conduct at a faster velocity per I μ. diameter than those of either the rabbit, the guinea-pig or the rat