Histologic and physiologic evaluation of electrically stimulated peripheral nerve: Considerations for the selection of parameters

Abstract

Helical electrodes were implanted around the left and right common peroneal nerves of cats. Three weeks after implantation one nerve was stimulated for 4-16 hours using charge-balanced, biphasic, constant current pulses. Compound action potentials (CAP) evoked by the stimulus were recorded from over the cauda equina before, during and after the stimulation. Light and electron microscopy evaluations were conducted at various times following the stimulation. The mere presence of the electrode invariably resulted in thickened epineurium and in some cases increased peripheral endoneurial connective tissue beneath the electrodes. Physiologic changes during stimulation included elevation of the electrical threshold of the large axons in the nerve. This was reversed within one week after stimulation at a frequency of 20 Hz, but often was not reversed following stimulation at 50-100 Hz. Continuous stimulation at 50 Hz for 8-16 hours at 400 microA or more resulted in neural damage characterized by endoneurial edema beginning within 48 hours after stimulation, and early axonal degeneration (EAD) of the large myelinated fibers, beginning by 1 week after stimulation. Neural damage due to electrical stimulation was decreased or abolished by reduction of the duration of stimulation, by stimulating at 20 Hz (vs. 50 Hz) or by use of an intermittent duty cycle. These results demonstrate that axons in peripheral nerves can be irreversely damaged by 8-16 hours of continuous stimulation at 50 Hz. However, the extent to which these axons may subsequently regenerate is uncertain. Therefore, protocols for functional electrical stimulation in human patients probably should be evaluated individually in animal studies.

Trans-Spinal Direct Current Stimulation Alters Muscle Tone in Mice with and without Spinal Cord Injury with Spasticity

“…For example, hypotonia is commonly observed in cerebellar deficits (Gilman, 1969), spinocerebellar lesions (Subramony and Ashizawa, 1993), and developmentally delayed children (Shumway-Cook and Woollacott, 1985). Hypertonia is associated with many CNS disorders, including stroke (Burke et al, 2013) and spinal cord injury (SCI; Adams and Hicks, 2005). Hypertonia includes spasticity and rigidity, and is characterized by a velocity-dependent increase in tonic stretch reflexes (Lance, 1980) and increased muscle activity during passive stretch (Katz and Rymer, 1989).…”

“…Hypertonia includes spasticity and rigidity, and is characterized by a velocity-dependent increase in tonic stretch reflexes (Lance, 1980) and increased muscle activity during passive stretch (Katz and Rymer, 1989). Spasticity can range from mild to severe and can cause striking impairments in functional movement (Adams and Hicks, 2005). Pharmacological, surgical, and physical treatments to manage spasticity have at best short-term efficacy and are confounded by side effects (Gracies et al, 1997).…”

Neural interfaces for somatosensory feedback

“…Extraneural electrodes surround a peripheral nerve, but do not insert elements within the nerve, causing the least disturbance to the neural tissue. Circular, self-sizing electrodes, such as the spiral [86] and helical electrode [87], have been stable in clinical applications for decades [88][89][90]. A circular configuration has the minimum surface area to interact with the neural tissue.…”

Intraoperative neuromonitoring techniques in the surgical management of acoustic neuromas

“…44 In a cat study, investigators found that extended periods of high frequency stimulation caused greater injury and that pulsed stimulations can reduce the risk of damage. 2 Interestingly, Kartush et al 55 found that constant current stimulation can be safely applied in guinea pig models as long as the electrode is properly insulated to preclude shunting. In summary, low stimulus frequencies and pulsed stimulations can be applied clinically to minimize the risk of injury from overstimulation.…”