Organophosphorous neuropathy. I. A teased-fiber study of the spatio-temporal spread of axonal degeneraion

Abstract

The spatio-temporal spread of axonal degeneration in organophosphorous neuropathy has been studied by means of the teased-fiber technique. Young adult cats were given a single intraperitoneal injection of di-isopropylfluorophosphate (DFP) and were killed 14, 18, 20, 21, and 28 days later by intracardiac perfusion with aldehydes. The cats developed clinical signs of delayed neurotoxicity 16 to 18 days after DFP injection. A histologic survey of the central and peripheral nervous systems revealed that the topographic distribution of axonal degeneration was characteristic of a dying-back neuropathy. In teased-fiber preparations from the left recurrent laryngeal nerve, we found that the axonal degeneration was initially focal and nonterminal but that the axonal degeneration subsequently spread in a somatofugal direction to involve the entire distal axon. Nerve fibre varicosities and paranodal demyelination preceded the axonal degeneration. It is concluded that neurotoxic organophosphates induce a focal, distal but not terminal axonal degeneration. This "chemical transection" of the axon then precipitates wallerian degeneration of the more distal axon. Thus, the traditional hypothesis that dying-back neuropathies evolve from a retrograde axonal degeneration is not valid for organophosphorous neuropathy.