Safety of long-term electrical peripheral nerve stimulation: review of the state of the art.

BACKGROUND: Electrical stimulation of peripheral nerves is used in a variety of applications such as restoring motor function in paralyzed limbs, and more recently, as means to provide intuitive sensory feedback in limb prostheses. However, literature on the safety requirements for stimulation is scarce, particularly for chronic applications. Some aspects of nerve interfacing such as the effect of stimulation parameters on electrochemical processes and charge limitations have been reviewed, but often only for applications in the central nervous system. This review focuses on the safety of electrical stimulation of peripheral nerve in humans.

METHODS: We analyzed early animal studies evaluating damage thresholds, as well as more recent investigations in humans. Safety requirements were divided into two main categories: passive and active safety. We made the distinction between short-term (< 30 days) and chronic (> 30 days) applications, as well as between electrode preservation (biostability) and body tissue healthy survival (harmlessness). In addition, transferability of experimental results between different tissues and species was considered.

RESULTS: At present, extraneural electrodes have shown superior long-term stability in comparison to intraneural electrodes. Safety limitations on pulse amplitude (and consequently, charge injection) are dependent on geometrical factors such as electrode placement, size, and proximity to the stimulated fiber. In contrast, other parameters such as stimulation frequency and percentage of effective stimulation time are more generally applicable. Currently, chronic stimulation at frequencies below 30 Hz and percentages of effective stimulation time below 50% is considered safe, but more precise data drawn from large databases are necessary. Unfortunately, stimulation protocols are not systematically documented in the literature, which limits the feasibility of meta-analysis and impedes the generalization of conclusions. We therefore propose a standardized list of parameters necessary to define electrical stimulation and allow future studies to contribute to meta-analyses.

CONCLUSION: The safety of chronic continuous peripheral nerve stimulation at frequencies higher than 30 Hz has yet to be documented. Precise parameter values leading to stimulation-induced depression of neuronal excitability (SIDNE) and neuronal damage, as well as the transition between the two, are still lacking. At present, neural damage mechanisms through electrical stimulation remain obscure.