title: Simulating mild systematic and focal demyelinating neuropathies: membrane property abnormalities.
abstract: This study provides numerical simulations of some of the abnormalities in the potentials and axonal excitability indices of human motor nerve fibers in simulated cases of internodal, paranodal and simultaneously of paranodal internodal demyelinations, each of them systematic or focal. A 70% reduction of the myelin lamellae (defining internodal demyelination), or of the paranodal seal resistance (defining paranodal demyelination), or simultaneously both of them (defining paranodal internodal demyelination) was uniform along the fiber length for the systematically demyelinated subtypes. These permutations were termed internodal systematic demyelination (ISD), paranodal systematic demyelination (PSD) and paranodal internodal systematic demyelination (PISD). In other tests, the same reductions of the myelin sheath parameters were used but restricted to only three (8th, 9th and 10th) consecutive internodes. Such fiber demyelinations were termed internodal focal demyelination (IFD), paranodal focal demyelination (PFD) and paranodal internodal focal demyelination (PIFD). The computations used our previous double cable model of the fibers. The axon model was comprised of 30 nodes and 29 internodes. The 70% reduction value was not sufficient to develop conduction block in all investigated demyelinations, which were regarded as mild. The membrane property abnormalities obtained in the ISD, PSD and PISD cases were quite different and abnormally greater than those in the IFD, PFD and PIFD cases. The changes in the excitability indices such as strength-duration time constants, rheobasic currents and recovery cycles in the focally demyelinated subtypes were so slight as to be essentially indistinguishable from normal values. Consequently, the excitability based approaches that have shown strong potential as diagnostic tools in systematically demyelinated conditions may not be useful in detecting mild focal demyelinations. The membrane property changes simulated in the systematically demyelinated subtypes are in good accordance with the data from patients with Charcot-Marie-Tooth disease type 1A (CMT1A) and chronic inflammatory demyelinating polyneuropathy (CIDP). The excitability abnormalities obtained in each focally demyelinated subtype match those observed in vivo in patients with demyelinating forms of Guillain-Barré syndrome (GBS). The results indicate that the model that was used is a rather promising tool in studying the membrane property abnormalities of hereditary, chronic and acquired demyelinating neuropathies, which up till now, have not been sufficiently well understood.
authors.affiliation: Institute of Biophysics, Bulgarian Academy of Sciences, Acad. G. Bontchev Str., Bl. 21, Sofia 1113, Bulgaria. dsteph@shiva.bio.bas.bg
authors.forename: D I
authors.initials: DI
authors.lastname: Stephanova
authors.forename: A S
authors.initials: AS
authors.lastname: Alexandrov
mesh_terms: D000200:Action Potentials / Q000502:physiology; D003198:Computer Simulation; D004558:Electric Stimulation / Q000379:methods; D006801:Humans; D008564:Membrane Potentials / Q000502:physiology*; D008959:Models, Neurological; D009413:Nerve Fibers, Myelinated / Q000473:pathology / Q000502:physiology*; D009431:Neural Conduction / Q000502:physiology; D011129:Polyradiculoneuropathy / Q000473:pathology* / Q000503:physiopathology*; D011930:Reaction Time