Development of the BION^â Microstimulator for Treatment in Obstructive Sleep Apnea.

Ross Davis*, Gregoire Cosendai, Isabel Arcos, Douglas Kushner, Delta Mishler, Christopher Decker, Anne-Marie Ripley, Dennis Maceri, Donna Sanderson, Yitzhak Zilberman, Joseph Schulman.

Alfred Mann Foundation, 28460 Av. Stanford, Valencia, California, 91355.

The BION^â system is a wireless network of up to 255 single-channel implantable microstimulators controlled and powered by an RF link from the BION^â Control Unit (BCU). Each stimulator is encased by a ceramic cylinder capped with an iridium cathode and an anode of platinum-iridium. The BION^â device is 16.7 mm long and 2.4 mm in diameter. Each stimulator produces asymmetric biphasic capacitively-coupled constant-current pulses. Pulse width (0 to 500 µsec), pulse amplitude (0 to 40 mA) and pulse frequency (0 to 600pps per BION^â, with 3,472 pps shared among all active BION^â microstimulators) are controlled digitally and powered by the controller via a 2 MHz AC magnetic link.

Microstimulator

The BION^â external system (BES) system was designed to provide a fitting interface running on a PC and a battery-operated control unit (BCU) that can independently operate up to 8 BION devices via a transmitting antenna. The BCU operates in two modes, connected to a PC for fitting purposes and Stand-Alone to allow the user to be independent. In Stand-Alone mode three sets of stimulation can be selected. The flexibility of the BES allows the user to generate various forms of bursts. The usual form of burst is composed of ramp-up, burst-on and burst-off, repeated as needed.

Obstructive Sleep Apnea (OSA) affects 2-4% of the U.S. population, causing up to 60 apneic episodes/hour. The main cause is the compromised pharyngeal airway by the tongue during sleep, especially R.E.M. sleep. Our aim is to introduce 1-2 BION^â devices on each side adjacent to the hypoglossal nerve (HGN), to cause contraction of the genioglossal muscle, to open this compromised airway during sleep.

Sheep Study:

To test the feasibility of this procedure, implantation of 28 functional BION^® microstimulators was completed into 7 adult sheep using a minimally invasive surgical technique. Through a 5 mm neck incision, a stimulating electrode probe was used to find the HGN in the lower jaw. A tailored plastic introducer (dilator + sheath) was then used to insert and test the position of the BION^® device before depositing it adjacent to the nerve. The BION^â device could be retrieved up to the next 7-10 days by reopening the small wound and withdrawing a subcutaneously placed suture attached to the superficial end of the device, which could then be reinserted. Two sheep (8 BION^® devices) died prematurely due to pneumonia unrelated to the implantation. The remaining 5 sheep with 20 BION^® devices were evaluated for stimulation thresholds over the long-term. Nine of 10 anteriorly inserted devices and 4 of 10 posteriorly placed were found to be consistently below 30mCoul./sq.cm./phase and stable over the 93-163 days studied. The other 7 (1 anterior, 6 posterior) were of higher thresholds and generally had lower stability. Electrode-to-nerve distances in 2 sheep (8 implants) showed a direct correlation to threshold values. The anterior neck approach to the HGN provided a closer and thus lower and more stable stimulation threshold level. Separately, histological evaluation of tissues subjected to higher stimulation showed no chronic tissue damage. Initial histological results revealed an average tissue capsule of 0.163mm (s.d.= 0.115mm).

Cadaver Study and Implant Procedure:

To further evaluate this surgical technique, in August 2002, a fresh cadaver with a 49 cm (19½ inch) neck circumference had the left hypoglossal nerve exposed through a 5 cm incision, at a depth of 3 cm approximately. Moving to a different location, the above described insertion technique was used through an anterior midline approach at 1 cm above the hyoid, angled left at 15 degrees to a depth of 4 cm. Upon reopening the initial incision on the left side, the cathode of the BION^â device was found to be lying adjacent to the HGN.

In order to test the functionality and reliability of the BES to control BION^â devices implanted in the lower jaw, one BION^â device with attached wires was placed adjacent to the hypoglossal nerve and its stimulation output was monitored. The antenna was placed under the chin using a garment specifically designed for the sleep apnea application that holds the antenna in the optimal anatomical position for driving BION^â devices.

System Testing:

The results on the cadaver test showed that the BION^â External System was capable of delivering enough power to BION^â devices inserted adjacent to the hypoglossal nerve. The BION^â device was capable of reaching stimulation parameters as high as 10 mA, 200 us, 20 pps, which was reliable, even under antenna displacements of up to 4 cm contra‑laterally to the anterior BION^â implantation site.

Based on the above in-vivo and cadaver studies and based on additional in-vitro qualification studies, we are submitting an FDA IDE for the treatment of obstructive sleep apnea by using the BION^â system; this is in conjunction with one of the primary U.S. sleep disorders research centers.

[BION^â is a registered trademark of Advanced Bionics Corporation, Valencia, CA.]

Acknowledgements to P. Mobley, K. Fey, D. Canfield, C. Byers, C. Tanacs, M. Vogel, M. Chamberlain, D. Richards, N. Embrey and J. Adomian for their considerable contributions.