The value of neuromodulation devices is that they offer a “third option” in the treatment of neurological disorders — one that can provide drug-free relief from symptoms while doctors work to assess the underlying cause. According to the International Modulation Society (IMS), “conventional medicine often uses the biomedical model of disease management whereby the underlying cause is searched for and treated to relieve symptoms. Neuromodulation involves directly treating the nervous system itself, often through small implanted devices that target a specific area, to rebalance the activity of neural circuits and manage symptoms as varied as severe unremitting neuropathic pain to severe movement disorders such as Parkinson's disease, or urinary or fecal incontinence due to overactive bladder or pelvic floor injury.” IMS notes that another area of interest — and a goal of the National Institute of Neurological Disorders and Stroke — is the development of totally implantable systems for restoring motor control and sensory feedback for paralyzed individuals.

IMS attributes the growth of the neuromodulation market to advances in neuroscience capabilities, including advances in miniaturization. As technology advances and new therapies require greater sophistication, new technologies are needed to support them. This article explores the dynamics driving the growth of this market and examines new technologies that have been developed to support the next generation of neurostimulation devices.

The global neurostimulation devices market is expected to register a CAGR of 12.5 percent between 2018 and 2023, according to a report from market research firm Modor Intelligence. North America leads this market because it has a well-established healthcare infrastructure with a high adoption rate of new technologies and innovation in neurological devices.1 A recent report from Grand View Research says this growth means that medical device manufacturers will “participate in rigorous R&D exercises to develop new products enabled with advanced technologies.” In addition, the report says that the introduction of technological advancements in neurostimulation, such as minimally invasive transdermal neuromodulation technology by companies like Neurowave Medical Technologies, are expected to result in immense growth of the market.2

Neuro: Addressing the Opioid Crisis

Neurostimulation devices are being called on to battle the opioid crisis — both as a treatment for opioid addiction and as an alternative to opioids for pain relief. In November 2017, FDA granted a new indication to an electrical stimulation device for use in helping to reduce the symptoms of opioid withdrawal. Opioid withdrawal causes acute physical withdrawal symptoms including sweating, gastrointestinal upset, agitation, insomnia, and joint pain. Electrical stimulation has few side effects and does not lead to addiction in the way that drugs do. This benefit will likely expand the use of nondrug options and continue the improvements made in the active implantables space.

“Given the scope of the epidemic of opioid addiction, we need to find innovative new ways to help those currently addicted live lives of sobriety with the assistance of medically assisted treatment. There are three approved drugs for helping treat opioid addiction. While we continue to pursue better medicines for the treatment of opioid use disorder, we also need to look to devices that can assist in this therapy,” says FDA Commissioner Scott Gottlieb, MD. “The FDA is committed to supporting the development of novel treatments, both drugs and devices, that can be used to address opioid dependence or addiction, as well as new, non-addictive treatments for pain that can serve as alternatives to opioids.”

One such device, the NSS-2 Bridge, is a small electrical nerve stimulator placed behind the patient's ear. It contains a battery-powered chip that emits electrical pulses to stimulate branches of certain cranial nerves. According to Indiana-based Innovative Health Solutions (IHS), which makes the device, such stimulation may provide relief from opioid withdrawal symptoms. The company says that patients can use the device for up to five days during the acute physical withdrawal phase.

Another application of neuromodulation devices is as an alternative to opioids for pain relief. One example is the SPRINT PNS System, which includes a proprietary lead and a small, wearable stimulator patch. The lead is placed percutaneously, or through the skin, and connects to the wearable stimulator, which activates peripheral nerves to achieve pain relief. “Opioids are routinely provided for several weeks to manage postoperative pain with approximately 20 percent of patients using them for 90 days or longer after surgery,” says Maria Bennett, SPR Therapeutics founder, president, and CEO. The company conducted a study in 2017 that reinforced the need for alternative, non-narcotic pain relief therapies. Bennett says that the device could significantly reduce or even eliminate the use of opiates, providing a much-needed medical advance for patients during the post-operative recovery period. Results of the study were published in Reconstructive Review, the official journal of the Joint Implant Surgery and Research Foundation.

SPRINT was specifically designed to preferentially activate target nerve fibers, delivering sustained, significant pain relief without opioids, permanent implants, or tissue destruction. The FDA-cleared therapy was developed to address a wide spectrum of chronic and acute post-surgical pain conditions. SPRINT's threadlike MicroLead is placed percutaneously using a 20-gauge introducer and then connected to the small wearable SPRINT stimulator. The lead is withdrawn without surgery at the end of the 60-day treatment period. The device delivers neurostimulation benefits without requiring a permanent implant.3

To spur the development of more of these types of devices, FDA has launched an innovation challenge for industry to develop devices, including digital health and diagnostic devices, to help combat the opioid crisis and to help prevent and treat Opioid Use Disorder — a serious health condition that can be a devastating outcome of opioid drug use.

The agency says this challenge is an example of its commitment to an “all-of-the-above” approach to more forcefully confront the opioid epidemic, including helping those currently addicted to opioids and preventing new cases of opioid addiction.” This effort seeks to provide device developers an opportunity to work directly with FDA to accelerate the development of innovative products, such as diagnostics to identify patients at increased risk for addiction, non-opioid pain therapies for acute or chronic pain, treatments for opioid use disorder or symptoms of opioid withdrawal, as well as devices that monitor the use and prevent diversion of prescription opioids. Breakthrough Device designation will be granted to those devices that meet the statutory criteria for designation without submission of a separate application.4

Brain-Controlled Prosthetics

Implantables are also making their mark in the field of prosthetics. Braingate, a consortium of academic and government institutions, is focused on researching and developing devices that use brain-computer interface (BCI)-driven muscle activation. The group defines these devices as “intra-cortical implants that pick up electrical neural activity in the brain and send that information to a computer, where the signals associated with intended movements are decoded. The computer then sends electrical impulses to muscles via implanted stimulating electrodes, which induce limb movement.”

One example is a modular prosthetic limb developed by the Johns Hopkins University Applied Physics Laboratory that is controlled by signals from surgically implanted electrodes. The patient's neurosurgeon placed an array of 128 electrode sensors — all on a single rectangular sheet of film the size of a credit card — on the part of the man's brain that normally controls hand and arm movements. Each sensor measured a circle of brain tissue 1 mm in diameter. The researchers turned on the prosthetic arm, which was wired to the patient through the brain electrodes, and asked the subject to “think” about individually moving thumb, index, middle, ring, and pinkie fingers. The electrical activity generated in the brain moved the fingers.5

A research group at the BRAIN (Building Reliable Advances and Innovation in Neurotechnology) Center at the University of Houston is also examining the responses of the nervous system to external stimulation through a wide array of devices, ranging from implantable micro electrodes for the nerve or central nervous system to deep brain stimulation. The work supported by the BRAIN Center, which involves industry and clinical partners, includes testing technologies designed to improve a range of the sensory, motor, and cognitive functions, such as those that researchers want to put into new kinds of prosthetic devices.

Building the Next Generation of Neuro Devices

Smaller, more easily implanted devices that don't sacrifice performance are the sweet spot of active implantables. Smaller subsystems drive smaller implants. For instance, devices implanted in the cranial space require very thin profiles. The primary areas that will benefit from smaller devices are cochlear applications and anything implanted in the cranial space, including those used for controlling prostheses. Therapies that use deep brain stimulation, for example, could be implanted in the head and eliminate the need for long leads to be tunneled through the neck, reducing a failure potential. Implants that are smaller can have greater placement flexibility without producing visual side effects.

Active implantable medical connectors have typically required serial arrays that allow for several connections in a row. As technology advances and new therapies become more sophisticated, the typical connection systems may not be able to support some of the new therapies that require a high number of electrodes or connection nodes.6 A new technology developed by Bal Seal Engineering, Foothill Ranch, CA, addresses these limitations. The high-density (HD) connectivity of the new connector array, which leverages the company's established Bal Conn® electrical contact technology, helps reduce neuro device size.

In cochlear therapies, where small implantable device sizes are critical, designers are considering new approaches to header connections. Here, Bal Conn® electrical contacts are vertically stacked in a high density configuration that boosts functionality and saves space. (Credit: Bal Seal Engineering)

The stacked configuration of the HD array allows for close pin configurations while maintaining isolation of the signals. If the system can support the alternative integration and lead interface, the HD array uses less space than other currently available systems. Its construction allows a tightly configured multi-polar pin to interface with corresponding connectors in a very small footprint. Ideal for cochlear systems that require up to 28 connections in a small cranial pocket, the technology can support profiles with connector ODs as small as 2.03 mm (0.080 in.) and pin/male interface diameters down to 0.7 mm (0.028 in.). Unlike typical active implant serial lead systems, the HD array produces a very dense vertical pin interface instead of the typical serial lead system. The HD array's vertical pin-and-socket configuration connects perpendicular to a typical serial system.

For manufacturers of devices used to deliver neuromodulation therapies, package size reduction is a constant challenge. But for neuro devices that are better suited to a more typical serial array, the SYGNUS® Implantable Contact System combines the company's Bal Conn® electrical contact technology with proven implantable-grade silicone isolation seals, resulting in a densely spaced connector stack that can accommodate lead diameters down to 0.9 mm (0.035 in.). The system's contact element consists of a housing made from medical-grade MP35N® and a platinum-iridium or MP35N® Bal Spring® canted coil spring. The spring contact offers low insertion force, provides multi-point conductivity, and compensates for both misalignment and mating surface irregularities. Because SYGNUS offers such a small pitch and combines both isolation seals and electrical contacts into a dense, configurable stack, it allows for a greater number of contacts to be used. The result is a decrease in overall device volume and an increase in functionality.

As neuro devices are designed to be smaller and last longer in the body, the overall dimensions of existing receptacles also pose manufacturing challenges. In such cases, the alternative orientation of the HD array system allows tight spacing in the smallest conditions, and this combination provides the opportunity for improved connection density. The system also eliminates the difficulty of smaller and smaller serial leads that need to travel through many seals and connections. Because forces build up as these leads travel through all of the connections, the lead flexibility makes it difficult to insert them as connection counts increase. The HD array addresses insertion force issues in serial arrays with small leads: the system has small short pins that have a larger grip position in the header cap to support ease of insertion.

Typical connection systems cannot support some of the emerging therapies that require a high number of electrodes or connection nodes. By contrast, the HD array supports these new therapies and can reduce connector space in a system. The minimized condition and performance support high connection count systems trying to address function and space. Increasing functionality means allowing a higher number of connections in a given space to enable the device to have closed loop functionality. The HD array can be customized to accommodate an OEM's proprietary design, and OEM-defined conditions drive the final design and integration of the connector systems. Exterior modifications can be accommodated to support weld requirements, and materials can be selected to support corrosion concerns. Pin design can also be modified to support connector demands.

Conclusion

Neuromodulation devices treat the nervous system itself, often through small implanted devices that target a specific area to manage a growing number of symptoms and disorders. These devices are also leading to innovative therapies to address the opioid crisis and new possibilities for people who rely on prosthetics. The growing neuromodulation market is being driven by technological innovations, including great advances in miniaturization. As implantable devices get smaller, options such as the 0.9 mm SYGNUS and the HD array, with its tightly configured multi-polar pin to interface with corresponding connectors, support the development of the next generation of neurostimulation devices.

This article was written by Mark Russell, Senior Global Market Manager - Medical Electronics for Bal Seal Engineering, Foothill Ranch, CA. For more information, visit here .


Medical Design Briefs Magazine

This article first appeared in the October, 2018 issue of Medical Design Briefs Magazine.

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