Systems and methods for selective peripheral nerve regeneration and remyelination

A neurostimulation system configured to promote axonal regeneration and remyelination repair of a peripheral nerve, comprising:

• (a) an electrode sized to couple to a peripheral nerve or distal branch that define a target nerve, the target nerve having a diameter of between about 1 mm and 25 mm, and having insulation configured to confine current to the target nerve;
• and
• (b) a controller programmed to deliver charge-balanced biphasic pulse trains having:
• a frequency between about 20 Hz and 100 Hz,
• a pulse width between about 150 microseconds and 500 microseconds,
• an interphase interval between about 25 microseconds and 100 microseconds,
• a train duration between about 3 seconds and 60 seconds, and
• rest intervals between about 0.5 minutes and 5 minutes,
• in one or more pulse trains per session, at least one session per day, on 1 to 7 days per week, for at least 2 weeks up to 20 weeks,
• the controller being further configured to set amplitude relative to a threshold appropriate for the nerve type comprising at or above contraction threshold for a motor nerve, below or near sensation threshold for a sensory nerve, or at a physiological threshold for an autonomic nerve.

A neuromodulation system that has a neuromodulation device configured to mechanically couple in direct contact with a distal peripheral nerve branch having a diameter between 0.5 millimeters and 3 millimeters, the neuromodulation device including a first electrode and a second electrode arranged as an active-return pair with a spacing of less than 1.5 millimeters, the neuromodulation system further having a controller configured to deliver stimulation to the distal branch at an amplitude less than 3 milliamps and to apply a therapy session that includes:

• pulse bursts each having a duration between 3 seconds and 45 seconds;
• a pulse frequency between 20 Hz and 80 Hz;
• a pulse width between 150 microseconds and 400 microseconds;
• a pulse-burst quantity between 1 and 6;
• and
• an inter-burst rest interval between 1 minute and 4 minutes;
• wherein the amplitude is selected based on a threshold of the distal branch, and
• wherein the stimulation produces selective activation of the distal branch while maintaining off-target activation below a contraction threshold, sensation threshold, or autonomic physiological threshold of adjacent nerves.