Differences in potentials and excitability properties in simulated cases of demyelinating neuropathies. Part III. Paranodal internodal demyelination

ObjectiveThe aim of this study is to investigate the potentials (intracellular, extracellular, electrotonic) and excitability properties (strength–duration and charge–duration curves, strength–duration time constants, rheobasic currents, recovery cycles) in progressively greater degrees of uniform reduction (20, 50 and 70%) of the paranodal seal resistance and myelin lamellae along the fibre length.MethodsThree paranodally internodally systematically demyelinated cases (termed as PISD1, PISD2 and PISD3, respectively) are simulated using our previous double cable model of human motor nerve fibres.ResultsThe results conform that in the more severely demyelinated cases, the intracellular potentials are with significantly reduced amplitude, prolonged duration and slowed conduction velocity, whereas the electrotonic potentials show abnormally greater increase in the early part of the hyperpolarizing responses. The extracellular potentials indicate increased polyphasia in the PISD3 case. The strength–duration time constants are shorter and the rheobasic currents higher in the demyelinated cases. In the recovery cycles, the demyelinated cases have less refractoriness, greater supernormality and less late subnormality than the normal case.ConclusionsThe uniform reduction of the paranodal seal resistance and myelin thickness along the fibre length has significant effects on the potentials and excitability properties of the simulated demyelinated human motor fibres. Unexpectedly, the PISD fibres behave like paranodally demyelinated ones, since the myelin reduction increases slightly the effect of the paranodal demyelination on the nerve membrane properties. The study shows that the excitability properties in demyelinating neuropathies are much more largely determined by the paranodal changes than by the internodal changes.SignificanceThe study provides new and important information about the pathophysiology of human demyelinating neuropathies.