FDA Recalls Abbott Stimulators for Technical Malfunction

By Pat Anson, PNN Editor

After receiving reports of dozens of injuries, the Food and Drug Administration has issued a Class I recall for two models of implantable neurostimulators due to a technical malfunction. The recall affects over 155,000 of Abbott’s Proclaim and Infinity devices, which are primarily used in spinal cord and deep brain stimulation.

Although Class I recalls are the most serious type of recall because they may result in injuries or death, patients are not being advised at this time to have the devices surgically removed. The stimulators were implanted in some patients as far back as 2015.

The malfunction occurs when the devices are temporarily turned off when a patient is having magnetic resonance imaging (MRI). There have been 186 complaints of patients being unable to turn the devices back on once the MRI ends, resulting in a loss of therapy and 73 injuries. No deaths have been reported.

In July, Abbott sent an “urgent medical device correction” letter to healthcare providers who install the devices, to clarify instructions on how to exit MRI mode.

The letter also advises providers to tell patients not to delete their device controller’s connection to Bluetooth if a malfunction occurs, and to update their systems and consult with a physician before having an MRI scan.   

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Abbott estimates that only about 0.06% of the recalled devices malfunctioned, with 0.03% of them resulting in loss of therapy and additional surgery.   

The following devices are included in the recall:

• Proclaim XR 5 IPG Model 3660 (previously known as the ‘Proclaim 5 Elite IPG Model 3660’)

• Proclaim XR 7 IPG Model 3662 (Previously known as the ‘Proclaim 7 Elite IPG Model 3662’)

• Proclaim Plus 5 IPG Model 3670

• Proclaim Plus 7 IPG Model 3672

• Proclaim DRG IPG Model 3664

• Infinity 5 IPG Model 6660

• Infinity 7 IPG Model 6662

Implantable neurostimulators are an invasive treatment of last resort for people with chronic back, leg or head pain. The devices are surgically implanted near the spine or brain, and emit low-level electrical impulses to block pain signals.

About 50,000 spinal cord stimulators (SCSs) are implanted annually in the U.S. and their use is growing – in part because of the belief they’ll reduce the need for opioids and other pain therapies. A recent study found that many patients with stimulators did not reduce their use of opioids, epidurals, corticosteroid injections or radiofrequency ablation; and about one in five had complications so severe the devices had to be removed or revised.

A 2018 study found that SCSs have some of the worst safety records of medical devices tracked by the FDA. An FDA review of adverse events involving stimulators found that nearly a third were reports of poor pain relief. The review also identified nearly 500 deaths linked to the devices, along with nearly 78,000 injuries and 30,000 malfunctions.

Thinking Outside the Pill Box: Another Approach to Pain Management

By Alon Ironi, CEO, Theranica Bio-Electronics

Well into my adulthood, I struggled with chronic back pain. I took medication after medication, finding myself getting sucked into the habit of popping painkillers and wondering why my pain wasn’t healing. I eventually discovered the psychological and mental elements inherent in chronic pain, and shifted my approach to pain management, which rapidly cured my back pain.  

The holistic approach to healing pain has historically been ridiculed in the medical community, preventing many physicians from recognizing the legitimacy of alternative treatments. The time has come to evolve beyond just popping pills to treat pain, towards a biopsychosocial perspective.  

The discovery and introduction of penicillin in 1928, marked the very beginning of medication popularization in the West. The development of new medications – for a wide range of uses - has extended life span and improved quality of life.  Unfortunately, the benefits associated with medication have encouraged its frequent use for disorders it simply is not meant for, such as certain types of chronic pain.  

Medication overuse headache is one example where drugs intended to treat migraine and headache can, with excessive use, lead to the deterioration of the exact condition they are supposed to be treating. Medication is an incredible tool when used properly, but it’s not the only tool, and it can be seriously harmful when misapplied.

What is Pain and How Do We Treat It? 

Pain is a unique bodily experience that, unlike other disorders, indicates an underlying issue in one’s physiology. Pain is an alarm system. It tells us that something is wrong, and if we mask it without treating its underlying cause, we might cause a great disservice to our bodies.  

The use of medication to treat short-term acute pain, while a person simultaneously heals from the cause of that pain, like a pulled muscle or a tear in a tissue, makes sense. However, the use of medication in instances of chronic pain - pain that persists longer than three months - is problematic.  

Chronic pain is a debilitating condition that impacts an individual’s everyday life. From migraine to chronic knee pain to chronic back pain, the routine of normal life is disrupted. Often, this chronic pain had an initial cause, such as a surgery, fall or injury that has since healed, but the pain persists long after its source has disappeared. This type of pain, as Haider Warraich, a physician and clinical researcher at Harvard, so aptly puts it, is like “an overlearned traumatic memory that keeps ricocheting around in our brains, often long after the injury it rehearses has fully healed.” 

This perception of chronic pain has its roots in quite a controversial physician -the late Jon Sarno, MD, a professor of rehabilitation medicine in the 1980’s and 90’s. His theories, while not rigorously proven in formal clinical studies, were built upon anecdotal data from thousands of patients he treated during his lifetime and are still being explored today. They have jumpstarted a revolution in our understanding of pain.  

The biopsychosocial model focuses on illness as a complex interaction of chemical and electrical reactions that are induced by biological, psychological and social factors. Contemporary pain researchers, like Lorimer Mosely, a clinical scientist, have applied this model to pain, recognizing that pain is comprised of both physical sensation and emotional stimulus, such as the fear of pain itself.  

Pain is no longer perceived as entirely “physical” in nature. It is now understood to be exacerbated by the fear of tissue damage and the aversion to previously experienced pain. As clinical research develops and shifts its focus to a more biopsychosocial approach to illness and pain, doctors must re-evaluate their first-line treatment suggestions. 

Drug-Free Pain Management 

Based on this new perception of pain, several nonpharmacological treatment methods for pain management have been developed. One approach is a purely psychological treatment called cognitive behavioral therapy, a form of talk therapy that discourages negative thoughts associated with pain and trains people to adhere to thoughts that stimulate the body’s natural pain relief system. Another example of nonpharmacological pain treatment is massage therapy,  which addresses pain by releasing muscle tension.  

Neuromodulation is highly effective in treating certain pain disorders through the use of electrical stimulation to modulate pain pathways in the neural system.  Several forms of neuromodulation treatment exist today, with different mechanisms of action and efficacy.  

Spinal cord stimulation, for example, is used to treat back pain and leg pain. But it is highly invasive, with electrodes surgically placed near the spinal cord to send electrical currents to the spine.

Deep brain stimulation is being studied for the relief of chronic pain, but it is also quite invasive, as it involves implanting electrodes into the brain.  

Nerivio is a non-invasive, wearable neuromodulation device made by my company that is FDA-approved for the treatment of acute migraine. Nerivio is self-applied to the upper arm, where it uses remote electrical neuromodulation (REN) to stimulate analgesic neurotransmitters in the pain pathways of migraine. In clinical trials, Nerivio and other REN devices have been shown to be just as effective as pharmacological treatments.  

To be clear, medication is a necessary and beneficial tool for treating infections, reducing fever, managing sickness and much more. However, its use in chronic pain management is sometimes misplaced, especially at a time when newer non-drug therapies are emerging.  

The holistic approach to pain management is the future. It considers the balance and context of a patient’s life and combines multiple modalities for their treatment. People are multifaceted and their treatment should be multifaceted as well. It is my hope and vision that this field of research will continue to develop and will soon be widely embraced by most medical professionals.  

Having experienced the benefits of drug-free pain management first-hand, I truly hope that health care systems will support patients in accessing these much-needed alternative treatments to improve quality of care and life.  

Alon Ironi is the CEO and co-founder of Theranica Bio-Electronics, the developer of Nerivio.

Alon received a Master of Science in Electrical Engineering from Santa Clara University, and a Bachelor’s of Science in Electrical Engineering from the Technion- Israel Institute of Technology.

Neuromodulation Device Effective for Most Migraine Sufferers

By Pat Anson, PNN Editor

A wearable neuromodulation device significantly reduced headache pain in nearly two-thirds of migraine sufferers, according to a new study. About one in four participants (22.6%) who used the device had no migraine pain after two hours.

The study findings, published in the journal Frontiers in Pain Research, are based on an analysis of over 23,000 remote electrical neuromodulation (REN) treatments with Nerivio, a device worn on the upper arm that uses mild electrical pulses to disrupt pain signals.

It’s important to note the study was designed and funded by Theranica Bio-Electronics, Nerivio’s manufacturer. Three of the five co-authors are Theranica employees.

“The current analysis of a very large group of patients, over a long period of time and multiple treatments, reinforces that REN provides a safe, efficacious and stable treatment option for acute treatment of migraine, both as a standalone and as an adjunct therapy. This is a very important component in the migraine therapy toolbox," lead author Jessica Ailani, MD, Director of the MedStar Georgetown Headache Center and Professor of Clinical Neurology, said in a press release.

Nerivio is controlled by a smartphone app that allows patients to set the intensity of their 45-minute treatments at the onset of a migraine. The app also has a migraine diary that allows patients and their doctors to track the effectiveness of REN.

It is from this app that study data was collected from 12,151 U.S. patients from 2019 to 2021. Most had been prescribed REN by headache specialists, indicating their migraines were difficult to treat with pain medication alone. During the study, about two-thirds of patients only used REN, with the remainder continuing to use over-the-counter or prescription medications.

"To the best of our knowledge, this study is the largest prospective real-world evidence analysis of a migraine device to date," said Alon Ironi, CEO of Theranica.

Migraine affects more than 37 million people in the United States, according to the American Migraine Foundation. In addition to headache pain, migraine can cause nausea, visual disturbances, and sensitivity to light and sound. Women are three times more likely to suffer from migraines than men.

Although migraine sufferers have many new treatments available, such as CBD oil and calcitonin gene-related peptide (CGRP) inhibitors, many find them too expensive or ineffective. Theranica hopes Nerivio can help fill the treatment gap, either as a standalone replacement for medication or as an adjunct.

"While some people with migraine get relief from prescribed or even over-the-counter medications, others do not respond to medications, or cannot tolerate their side effects. There are also people who cannot use medications due to contraindications or being at risk of drug-drug interactions or medication overuse headache,” Ailani said.

The FDA approved Nerivio as a treatment for acute migraine in adults in 2019. Last year the label was expanded to include children over the age of 12 with episodic or chronic migraine. Over 25,000 people in the U.S. have used the device, according to Theranica.

Nerivio is only available by prescription. When purchased wholesale, the listed price is $599 for a twelve-treatment unit, although buyers can save money by enrolling in a patient savings program, depending on their insurance coverage.  

A New Option for Young Migraine Sufferers

By Pat Anson, PNN Editor

Migraines can have a devastating impact on children and adolescents. In addition to causing head pain, upset stomachs and visual disturbances, migraine attacks can disrupt school and social activities at a sensitive time in a young person’s life.

Although pediatric migraines are common, affecting about 10% of school-age children and one in five teenagers, treatment options are very limited compared to adults. There are no FDA approved pharmaceutical migraine treatments for kids under the age of 12. That leaves doctors to prescribe migraine medication to children off-label, including a new class of migraine drugs called CGRP inhibitors, which have not yet been approved or studied in young children. 

A small new study suggests there may be a safer and more effective option for young migraineurs: neuromodulation. Research recently published in the journal of Pain Medicine found that Nerivio, a neuromodulation device worn on the upper arm, was more effective in treating acute migraine in adolescents than triptans and over-the-counter pain relievers. Nerivio uses smartphone-controlled electrical pulses to stimulate nerves and disrupt pain signals.

“To my knowledge, this is the first study that directly compared remote electrical neuromodulation and standard-care treatment options in adolescents,” says lead author Andrew Hershey, MD, co-director of the Headache Center at Cincinnati Children’s Hospital Medical Center.

“Migraine in adolescents is associated with poorer performance and absence from school and social activities during a particularly formative time in life. Providing teens with more effective and engaging treatments for migraine can have far-reaching positive effects over the course of their lives.”

Nerivio was developed by Theranica, an Israeli medical technology company that sponsored the study. The FDA approved the device as a treatment for acute migraine in adults in 2019 and recently expanded the label to include children over the age of 12 with episodic or chronic migraine.

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Thirty-five adolescent migraine patients aged 12 to 17 took part in the two-month comparison study. Over-the-counter drugs and oral triptans were used by patients during the medication month, and Nerivio during the Remote Electrical Neuromodulation (REN) month.

Two hours after treatment, over a third (37%) of patients achieved complete pain freedom during the REN phase of the study, compared to just 8.6% in the medication phase. Some degree of pain relief was reported by 80% of patients in the REN phase, as opposed to 57% in the medication phase.

“This study provides evidence that Nerivio may be considered as a first-line acute treatment, especially for adolescents with medication restricting comorbidities or a preference for a non-medication-based treatment,” said co-author Samantha Irwin, MD, a pediatric neurologist at the UCSF Benioff Children Hospital in San Francisco. “The importance of having a non-pharmacologic, discrete, easy-to-use and effective acute treatment in the adolescent armamentarium cannot be overstated.”

Long-Term Effects of Childhood Migraine

Early treatment of childhood migraine is important because there is emerging evidence that repeated headache attacks in children reduce the formation of “gray matter” in parts of the brain that process pain signals, leading to more frequent and severe migraines in adults.   

“We’ve done studies here independent of any pharmaceutical company where we’ve show that the earlier we can intervene with effective therapy and education of patients, the better their long-term outcome,” Hershey told PNN. “So we really have this opportunity to intervene with a child or adolescent that can affect them for their life.

“A device can be as effective as a drug. What I tell patients is that it gives them their own locus of control. Instead of taking a medication and hoping it works, they’re actually controlling the device with their smartphone, and so they can really take control of their headaches, which is ultimately what we want them to do.”    

Nerivio is only available by prescription and is eligible for insurance. When purchased wholesale, the listed price is $599 for a twelve-treatment unit, although buyers can save money by enrolling in a patient savings program, depending on their insurance coverage.  

Theranica is currently recruiting patients for a placebo-controlled study to see if Nerivio may be effective in preventing migraines. The company is also investigating whether the device may help treat other chronic pain conditions besides migraine.

Migraine affects more than 37 million people in the United States, according to the American Migraine Foundation. In addition to headache pain, migraine can cause nausea, blurriness or visual disturbances, and sensitivity to light and sound. Women are three times more likely to suffer from migraines than men.

Pilot Study Shows Neuromodulation Effective for Postoperative Pain

By Pat Anson, PNN Editor

In recent years, many U.S. hospitals have adopted policies that reduce or eliminate the use of opioids after surgery. For some, that means giving their patients Tylenol or Lyrica for postoperative pain. For others, it means trying neuromodulation — a non-pharmacological therapy that new research shows may have some potential.

In a placebo-controlled pilot study led by researchers at University of California San Diego, patients who received percutaneous peripheral nerve stimulation (PNS) had significant reductions in their pain levels after outpatient joint surgery.

Percutaneous PNS is a form of neuromodulation that involves the placement of a tiny wire or “lead” alongside a peripheral nerve. The implanted lead is then connected to a small external pulse generator that sends a mild electric current to the nerve, interrupting pain signals. PNS has been used for years to treat chronic pain, but this was the first clinical trial to assess its use for postoperative acute pain.    

In the pilot study, 65 adult patients scheduled for operations on their shoulders, knees or ankles had leads placed before surgery in the affected joint. After surgery, half of the patients were given neuromodulation, while the other half received a "sham" treatment with a pulse generator that appeared active but did not deliver any electric current.

Patients in both groups received opioids as needed for their postoperative pain, and after one week their pain scores and opioid use were compared.

Researchers reported in the journal Anesthesiology that the results were “much greater than we had anticipated.” Pain scores were over 50 percent lower in patients who received neuromodulation. The mean pain score (on a zero to ten scale) was 1.1 in patients receiving PNS treatment, compared to 3.1 in the sham group.

Nerve stimulation was also associated with an 80 percent reduction in opioid consumption. The median opioid dose (oral morphine equivalent) in the first week after surgery was 5 milligrams in the active treatment group, compared to 48 milligrams in the sham group.

“This multicenter, randomized, double-masked, sham- controlled pilot study provides evidence that ultra-sound-guided percutaneous peripheral nerve stimulation concurrently improves analgesia and decreases opioid requirements to a statistically significant and clinically meaningful degree for at least a week after moderately to severely painful ambulatory orthopedic surgery,” wrote lead author Brian Ilfeld, MD, a professor of anesthesiology at UC San Diego.

Ilfeld and his colleagues say the pain-relieving benefits of neuromodulation continued after the leads were removed 14 days after surgery, but they appeared to wear off after one month. They plan on conducting a larger clinical trial with 250 surgery patients and to follow them for a year to see if there are any long-term benefits from neuromodulation.

Contrary to popular belief, opioid addiction is rare after surgery. A large 2016 study found only 0.4% of older adults were still taking opioids a year after major elective surgery. Another large study in 2018 found only 0.2% of patients who took opioids for post-surgical pain were later diagnosed with opioid dependence, abuse or had a non-fatal overdose.

Nevertheless, the now defunct American Pain Society (APS) released guidelines in 2016 that encourage physicians to use non-opioid medication such as acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs), gabapentin (Neurotin) and pregabalin (Lyrica) for post-operative pain. The APS also recommended non-pharmacological therapies such as cognitive behavioral therapy and transcutaneous elective nerve stimulation (TENS) as adjunct treatments.

The lead author of the APS guideline was Roger Chou, MD, who also co-authored the 2016 CDC opioid guideline.

‘Injectrode’ Could Revolutionize Neuromodulation Pain Treatment

By Pat Anson, PNN Editor

A team of scientists and engineers has developed a flexible electrode that can be injected into the body to stimulate damaged nerves, relieve chronic pain and treat other conditions.

The so-called “injectrode” could revolutionize neuromodulation therapy by eliminating the need for invasive spinal cord stimulators and other surgically implanted medical devices.

Researchers used a liquid silicone base -- similar to surgical glue – and mixed it with small metal particles to make it electrically conductive.

When injected around a nerve and allowed to cure, the injectrode performs much like a metal wire, but remains flexible.

Current neuromodulation treatments often rely on rigid implanted devices that can cost hundreds of thousands of dollars, require complex surgeries to install, and often fail or need to be replaced.

IMAGE COURTESY OF NEURONOFF

"Typical implants are really stiff, and so as the body moves, they wear and tear and break down. Our liquid cures, and the result is much closer to the normal elasticity of tissue. You can actually stretch it and increase its size 150 percent to 200 percent without losing its conductivity," says co-author Kip Ludwig, PhD, a professor of biomedical engineering and neurological surgery at University of Wisconsin-Madison.

“By virtue of its simplicity, the Injectrode has the potential to be less invasive, more robust, and more cost‐effective than traditional electrode designs, which could increase the adoption of neuromodulation therapies for existing and new indications.”

Ludwig and his colleagues reported their findings in the journal Advanced Healthcare Materials.

The injectrode has been tested on laboratory animals to stimulate their nervous systems. It was used in pigs to induce heart rate changes by stimulating the vagus nerve in the neck, an approach that's shown promise for treating heart failure, hypertension, lupus and cluster headaches.

"We essentially went through the standard repertoire of electrochemical tests to show this acts like a standard wire electrode that could be used to stimulate the nerve," says co-author James Trevathan, PhD, a postdoctoral fellow in Ludwig's lab.

Ludwig co-founded Neuronoff, a company based on the injectrode, with Case Western Reserve University biomedical engineering professor Andrew Shoffstall, PhD, and Neuronoff CEO Manfred Franke, PhD. Neuronoff recently secured a $2.1 million grant from the National Institutes of Health to further develop the injectrode to stimulate spinal nerves as a treatment for chronic back pain.

The researchers are testing a scheme in which they inject the fluid around the nerve, then extrude a thin insulated string of the material back to just underneath the surface of the skin, where they inject more of the composite material. Then they can use a basic transcutaneous electrical nerve stimulation (TENS) unit to stimulate the nerve from the surface of the skin.

"We're making a bypass from the surface of the skin to the location we want to stimulate," says Ludwig, who envisions using a robotic surgical system to install the injectrode in a procedure similar to getting a tattoo.

"As we learn more and more about how to interface with the nervous system, we're not limited to what we've implanted through an invasive surgical procedure. We can actually change how we stimulate, how we talk to the nerve, because we're essentially just routing our connection to this deep nerve back to the surface of the skin."

Spinal cord stimulators have some of the worst safety records among medical devices, according to a 2018 report by investigative journalists. Stimulators are often touted as safer alternatives to opioid pain medication, but a review of FDA data found over 500 deaths and 80,000 injuries involving stimulators since 2008. Patients reported being shocked or burned by the devices and many had them removed.  

FDA Clears New Wearable Device for Migraine

By Pat Anson, PNN Editor

A neuromodulation device worn on the arm and controlled by a smartphone has been cleared by the Food and Drug Administration for the treatment of acute migraine. The Nerivo Migra device was developed by Theranica, an Israeli medical technology company, and is expected to be available in the U.S. later this year.

The FDA’s market authorization is based on the results of a double-blind, placebo-controlled study of Nerivo Migra involving 252 migraine patients at 12 headache clinics in the U.S. and Israel. The study findings were recently published in Headache: The Journal of Head and Face Pain.

Over two-thirds of patients who wore the device for 30-45 minutes during a migraine attack experienced pain relief two hours after treatment, compared to only about a third of those who wore a sham device. For many, the pain relief was sustained 48 hours after treatment.

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"The results of the study demonstrate a high efficacy ratio for single as well as multiple attacks, both at two and 48 hours after treatment," said lead investigator Dr. Brian Grosberg, MD, director of the Hartford Healthcare Headache Center in Connecticut.

Placed on the upper arm, Nerivio Migra uses smartphone-controlled electrical pulses to disrupt pain signals. At this time, the device is only indicated for acute treatment of migraine with or without aura in adult patients who do not have chronic migraine. But company officials say it shows potential as a treatment for other pain conditions.

"We have identified at least 7 different painful conditions that may be relieved by this non-invasive, drug-free technology after appropriate clinical development," said Alon Ironi, CEO and co-founder of Theranica. "While the company is preparing to launch the Nerivio Migra in the United States market later this year at an affordable price, we remain committed to continuing our clinical development, expanding the use of remote electrical neuromodulation therapy for additional indications.”

Theranica has not disclosed what its “affordable price” will be. Over the next four months, the company said it would begin a series of clinical studies of Nerivo Migra at 30 headache clinics in the U.S. to assess patient selection and correct product use.

A handheld neuromodulation device – called gammaCore –  is currently available for about $600 to treat migraine and cluster headache.  Another device used to treat migraine – called Cefaly – is worn on the head and costs about $350. A new class of injectable migraine drugs is even more expensive, costing about $7,000 a year or $580 for each monthly dose.

"Over the last 20 years my colleagues and I have used triptans and ergots for acute migraine treatment. There is a large unmet need for new treatments in this population when these medications are not effective, are contra-indicated, or have non-tolerable side effects,” said Stephen Silberstein, MD, a member of Theranica’s medical advisory board.

“In addition, triptans and most current acute migraine medications, including over-the-counter drugs indicated for migraine, are associated with medication-overuse headache, which is associated with increased frequency of migraine attacks, and often results in chronic migraine.”

Migraine affects a billion people worldwide and about 36 million adults in the United States, according to the American Migraine Foundation. In addition to headache pain and nausea, migraine can cause vomiting, blurriness or visual disturbances, as well as sensitivity to light and sound. Women are three times more likely to suffer from migraine than men.