CMT1A: Simulating mild systematic and focal demyelinating neuropathies: membrane proper

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J Integr Neurosci. 2006 Dec;5(4):595-623.

Simulating mild systematic and focal demyelinating neuropathies:

membrane property abnormalities.

Stephanova DI, androv AS.

Institute of Biophysics, Bulgarian Academy of Sciences, Acad. G.

Bontchev Str., Bl. 21, Sofia 1113, Bulgaria.

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-Barre 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.