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Tissue Response:Nerve: Page 10

Axonal Damage.

“Salt & Pepper” appearance of peripheral nerve after stimulating at 50 Hz several hours. Axon with a filled appearance is believed to be damaged. This has been termed “early axonal damage”.

Agnew and McCreery interpret these data to indicate that protracted periods of stimulation at frequencies above 20 Hz can give rise to deleterious effects to the nerve fiber. The mechanism for this type of damage is not known.

Agnew et al. 1990, found that lidocane infused in the electrode eliminated the ESD signs. It is not known if the lidocane participated in the electrode electrochemistry.
Normalizing factor the stimulus current that is required to recruit fully the earliest a component of the compound action potential (CAP) induced by the stimulation. The a component of the CAP is composed of the action potentials from group I and group II efferent fibers as well as the afferent fibers that have overall diameters of approximately 5–22µm

 

The stimulus frequency was either 20, 50, or 100Hz. The abscissa of Figure 4.3 is the percentage of myelinated axons undergoing early axonal degeneration at 7 days after the stimulation [25]. It should be interpreted as a relative, rather than an absolute, scale of axonal injury since, during EAD, a particular myelinated fiber may appear quite normal at one point along the nerve (i.e. in a particular histological cross-section) but will appear markedly degenerated at another level [20]. When the stimulus frequency was 20Hz, there was virtually no axonal injury that could be attributed to the stimulation, even when the stimulus amplitude was eight times greater than that necessary to recruit fully the a component of the compound action potential; when the stimulus frequency was 50Hz, axonal damage occurred when the stimulus amplitude exceeded approximately one a unit; when the stimulus frequency was 100Hz, the threshold for the neural injury was nearly unchanged, but the slope of the regression line increased markedly.

 

 

 

 

 

TISSUE REACTION: SUMMARY
The mechanism of stimulation induced tissue damage is still unknown. Excessive neural activity and the toxic products of electrochemical reactions are two strong candidates. Heating and poreation are generally not considered viable candidates for inducing tissue injury under conditions that most neural prostheses operate.
Self-sizing cuffs such at the CWRU spiral cuff and the Huntington helical cuff are recommended.
Safe charge densities have not been worked out for peripheral nerve. However, one could use a number like 50 µC/cm2 as a maximum safe value, drawn from brain work.
Most of the work on peripheral nerve has been done in the framework of mass action causing the damage. These results indicate that intermittent stimulation (50 Hz with a 50% duty cycle) and continuous stimulation at 20 Hz can be tolerated at a stimulus amplitude that yields full activation of the large nerve fibers. In addition, continuous stimulation for less than four hours can be tolerated at 50 Hz. There has been no functional manifestation observed for animals exhibiting signs of EAD.

The dissection process, associated with mobilizing a peripheral in preparation for an electrode implant, has a 25% to 30% risk of inducing some trauma to axons. The myelin seems to be the most vulnerable and the source is believed to be ischemia induced during the dissection process. This suggests that care should be given to avoid manipulations that could compromise blood flow. Nerve fibers sustaining this type of damage appear to almost always recover normal function. Often there is no functional manifestation of the myelin insult.

Agnew, W.F., and D.B. McCreery. "Principles of safe and effective nerve stimulation", In: New perspectives in sacral nerve stimulation, edited by U. Jonas, and V. Grunewald. London: Martin Dunitz, 2002, pp. 29-42

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