Differences in Membrane Properties in Simulated Cases of Demyelinating Neuropathies: Internodal Focal Demyelinations without Conduction Block

Stephanova, D. I.; Daskalova, M.; Alexandrov, Alexandar

doi:10.1007/s10867-005-9001-9

Cited by 10 publications

(7 citation statements)

References 17 publications

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“…The uniformly reduced amplitudes, prolonged duration and slowed conduction velocities of the intracellular potentials are also characteristic of these abnormal cases. Furthermore, our previous study [17], investigating the membrane properties in simulated internodally focally demyelinated (IFD) cases without conduction block, shows that the changes in the excitability indices match those recorded in vivo in patients with Guillain-Barré syndrome. Both in patients and in the simulations, the changes are so slight that they are difficult or impossible to distinguish from normal values.…”

Section: Introductionmentioning

confidence: 80%

“…The strength-duration time constants and rheobasic currents are calculated by the method, which is described earlier [13][14][15][16][17] and, in brief, the threshold stimulus duration is increased in 0.025 ms steps from 0.025 ms to 1 ms, to obtain the strength-duration curves. A polynomial function of degree 2 (transfer standard parabola), which relates threshold charge (Q) to stimulus duration (t), provides an accurate fit of the data:…”

Section: Methodsmentioning

confidence: 99%

“…The findings may not necessarily be identical to those in human demyelinating neuropathies, which can be associated with additional factors such as activation of cytokines, complements or other inflammatory substances, resulting in dysfunction of ion channels, and macrophage invasion or nerve edema/fibrosis leading to structural changes. However, the simulated results [13][14][15][16][17] indicate that this model is a rather promising tool in studying the prominent features in neuropathies and neuronopathies which up till now have not been sufficiently well understood.…”

Section: Methodsmentioning

confidence: 99%

“…These indices, which depend on the biophysical properties of the axonal membrane and myelin sheath, can now be measured in healthy subjects and patients with demyelinating neuropathies [8][9][10][11][12]. Recently, the method of mathematical modelling has also been applied as a promising tool for studying excitability properties in nerve disorders [13][14][15][16][17]. Our previous study [16], investigating membrane properties in simulated cases of CMT1A, shows that greater negative electrotonic responses, longer strength-duration time constants, and greater refractoriness and supernormality in the recovery cycles can be used as specific indicators of internodal systematic demyelinations (ISD).…”

Section: Introductionmentioning

confidence: 99%

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Differences in Membrane Properties in Simulated Cases of Demyelinating Neuropathies: Internodal Focal Demyelinations with Conduction Block

Stephanova

Daskalova²,

Alexandrov³

2006

J Biol Phys

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Abstract. The aim of this study is to investigate the membrane properties (potentials and axonal excitability indices) in the case of myelin wrap reduction (96%) in one, two and three consecutive internodes along the length of human motor nerve fibre. The internodally focally demyelinated cases (termed as IFD1, IFD2 and IFD3, respectively, with one, two and three demyelinated internodes) are simulated using our previous double cable model of the fibre. The progressively greater increase of focal loss of myelin lamellae blocks the invasion of the intracellular potentials into the demyelinated zones. For all investigated cases, the radial decline of the extracellular potential amplitudes increases with the increase of the radial distance and demyelination, whereas the electrotonic potentials show a decrease in the slow part of the depolarizing and hyperpolarizing responses. The time constants are shorter and the rheobases higher for the IFD2 and IFD3 cases than for the normal case. In the recovery cycles, the same cases have less refractoriness, greater supernormality and less late subnormality than the normal case. The simulated membrane abnormalities can be observed in vivo in patients with demyelinating forms of Guillain-Barré syndrome. The study provides new information about the pathophysiology of acquired demyelinating neuropathies.

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Section: Introductionmentioning

confidence: 80%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Differences in Membrane Properties in Simulated Cases of Demyelinating Neuropathies: Internodal Focal Demyelinations with Conduction Block

Stephanova

Daskalova²,

Alexandrov³

2006

J Biol Phys

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“…Recently, a method of mathematical modeling has been used to simulate the above mentioned demyelinating neuropathies (Stephanova and Daskalova 2005a,b, Stephanova et al 2005, 2006a. In these studies, the fiber demyelinations are regarded as internodal, paranodal, and, simultaneously, paranodal internodal, each of them systematic or focal.…”

Section: Introductionmentioning

confidence: 99%

Simulating focal demyelinating neuropathies: membrane property abnormalities

et al. 2006

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Membrane properties such as potentials (intracellular, extracellular, electrotonic) and axonal excitability indices (strength-duration and charge-duration curves, strength-duration time constants, rheobasic currents, recovery cycles) can now be measured in healthy subjects and patients with demyelinating neuropathies. They are regarded here in two cases of simultaneously reduced paranodal seal resistance and myelin lamellae in one to three consecutive internodes of human motor nerve fiber. The investigations are performed for 70 and 96% myelin reduction values. The first value is not sufficient to develop a conduction block, but the second leads to a block and the corresponding demyelinations are regarded as mild and severe. For both the mild and severe demyelinations, the paranodally internodally focally demyelinated cases (termed as PIFD1, PIFD2, and PIFD3, respectively, with one, two, and three demyelinated internodes) are simulated using our previous double-cable model of the fiber. The axon model consists of 30 nodes and 29 internodes. The membrane property abnormalities obtained can be observed in vivo in patients with demyelinating forms of Guillain-Barré syndrome (GBS) and multifocal motor neuropathy (MMN). The study confirms that focal demyelinations are specific indicators for acquired demyelinating neuropathies. Moreover, the following changes have been calculated in our previous papers: (1) uniform reduction of myelin thickness in all internodes (Stephanova et al. in Clin Neurophysiol 116: 1153-1158, 2005); (2) demyelination of all paranodal regions (Stephanova and Daskalova in Clin Neurophysiol 116: 1159-1166, 2005a); (3) simultaneous reduction of myelin thickness and paranodal demyelination in all internodes (Stephanova and Daskalova in Clin Neurophysiol 116: 2334-2341, 2005b); and (4) reduction of myelin thickness of up to three internodes (Stephanova et al., in J Biol Phys, 2006a,b, DOI: 10.1007/s10867-005-9001-9; DOI: 10.1007/s10867-006-9008-x). The membrane property abnormalities obtained in the homogeneously demyelinated cases are quite different and abnormally greater than those in the case investigated here of simultaneous reduction in myelin thickness and paranodal demyelination of up to three internodes. Our previous and present results show that unless focal demyelination is severe enough to cause outright conduction block, changes are 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, independently of whether they are internodal, paranodal, or paranodal internodal.

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Membrane property abnormalities in simulated cases of mild systematic and severe focal demyelinating neuropathies

Stephanova

Daskalova

2007

Eur Biophys J

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The investigation of multiple nerve membrane properties by mathematical models has become a new tool to study peripheral neuropathies. In demyelinating neuropathies, the membrane properties such as potentials (intracellular, extracellular, electrotonic) and indices of axonal excitability (strength-duration time constants, rheobases and recovery cycles) can now be measured at the peripheral nerves. This study provides numerical simulations of the membrane properties of human motor nerve fibre in cases of internodal, paranodal and simultaneously of paranodal internodal demyelinations, each of them mild systematic or severe focal. The computations use our previous multi-layered model of the fibre. The results show that the abnormally greater increase of the hyperpolarizing electrotonus, shorter strength-duration time constants and greater axonal superexcitability in the recovery cycles are the characteristic features of the mildly systematically demyelinated cases. The small decrease of the polarizing electrotonic responses in the demyelinated zone in turn leads to a compensatory small increase of these responses outside the demyelinated zone of all severely focally demyelinated cases. The paper summarizes the insights gained from these modeling studies on the membrane property abnormalities underlying the variation in clinical symptoms of demyelination in Charcot-Marie-Tooth disease type 1A, chronic inflammatory demyelinating polyneuropathy, Guillain-Barré syndrome and multifocal motor neuropathy. The model used provides an objective study of the mechanisms of these diseases which up till now have not been sufficiently well understood, because quite different assumptions have been given in the literature for the interpretation of the membrane property abnormalities obtained in hereditary, chronic and acquired demyelinating neuropathies.

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Differences in Membrane Properties in Simulated Cases of Demyelinating Neuropathies: Internodal Focal Demyelinations without Conduction Block

Cited by 10 publications

References 17 publications

Differences in Membrane Properties in Simulated Cases of Demyelinating Neuropathies: Internodal Focal Demyelinations with Conduction Block

Differences in Membrane Properties in Simulated Cases of Demyelinating Neuropathies: Internodal Focal Demyelinations with Conduction Block

Simulating focal demyelinating neuropathies: membrane property abnormalities

Membrane property abnormalities in simulated cases of mild systematic and severe focal demyelinating neuropathies

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