Multidisciplinary U of M team builds on their previous research to help relieve a patient’s pain

Dr. Alex Herman (left) and Dr. David Darrow stimulate and record brain activity to improve April Reasor's pain.

Neurosurgeon David Darrow, MD, MPH, has spent the past five years working in collaboration with Tay Netoff, PhD, in Biomedical Engineering, to develop neurostimulation setting algorithms for Darrow’s E-STAND (Epidural Stimulation After Neurologic Damage) study. The goal of the study is to optimize the use of epidural spinal cord stimulation to restore voluntary movement in patients suffering from chronic spinal cord injury and paraplegia. The stimulation has been successful for some study participants, inspiring the team to patent their algorithms.

Then Darrow met April Reasor.

Dealing with chronic pain
April ReasorA resident of Grand Rapids, MN, April (pictured at left) had been trying to find relief for a facial pain condition that started in 2019 as the result of two thalamic strokes she suffered in 2014 and 2016. The left side of April’s face had become cold and numb. She also had constant pain on that side with intermittent “sharp, electrical pulses,” as she described them.

Her neurologist thought April had a facial pain condition known as trigeminal neuralgia. He prescribed medication typically used for that condition, but it had no effect. He then referred her to the U of M and neurologist Sarah Benish, MD, became part of April’s care team. “Dr. Benish recommended several treatments and kept checking on me, asking me how it was going,” said April. “I told her the condition continued to be debilitating.” Benish referred her to Darrow, who is part of the University’s Facial Pain Clinic.

Collaborating to give relief
David Darrow, MD, MPHDuring a telehealth visit with April, Darrow (pictured at left) told her he thought he might be able to help her. He knew that April had already tried all of the standard treatments – and many more – without any relief. Through his partnership with Department of Psychiatry and Behavioral Sciences psychiatrist Alex Herman, PhD, to study cognition and neuromodulation in the Herman Darrow Lab, Darrow was hopeful that he could help. The neurostimulation work he had been doing with Netoff and other studies published in the literature further convinced him. “Until Dr. Darrow, there wasn’t anyone who wanted to figure this out,” April said. “I had finally found someone willing to try and fix my problem and give me some relief.”

April has what is known as central post-stroke pain (CPSP). According to Darrow, CPSP is a condition that often develops after a stroke in the thalamus — a part of the brain that serves as a relay center through which sensory nerves transmit signals from the spinal cord and brainstem on the way to the cerebral cortex.

Pain from sensory deficit
“CPSP starts with numbness and progresses into uncontrollable pain due to the number of neurons that had been killed by the stroke,” Darrow explained. “Cutting sensory input like that triggers rampant hyperexcitability, which creates the perception of pain even though there is nothing actually going on.”

About 1 to 12 percent of stroke patients develop CPSP. “It’s a rare enough disease, though, that no one will get FDA approval for a treatment,” said Darrow. “It makes it challenging for neurosurgeons and pain doctors to treat people with an ‘orphan disorder’ like CPSP.”

Despite the challenges, Darrow worked with Netoff, and his colleagues from the Herman Darrow Laboratory, the Department of Anesthesia, and the Facial Pain Clinic (Neurosurgery and Dentistry), to create a treatment strategy for April.

Building on their foundation
Using the work already done to develop the neurostimulation setting algorithms, the team was going to take an innovative two-pronged approach to treating April’s pain via cortical brain stimulation. Darrow would implant two electrodes – one over the motor cortex and one over the dorsolateral prefrontal cortex. “We extended the motor cortex stimulation by adding another stimulator to the prefrontal cortex of the brain,” said Darrow. “Some transcranial magnetic stimulation studies have shown this would be a good place to manage pain. We were hoping to give April every possible option in as safe a manner as possible.”

Tweet about the bedside work with AprilThe day after the October 6, 2021, minimally invasive surgical procedure to implant the electrodes, Darrow and Netoff began working with April at her hospital bedside. They wanted her to choose the stimulation settings that gave her the most relief. “It was like going to the optometrist,” April said. “They asked me if setting 1 was better than setting 2, if setting 2 was better than setting 3, and so on.”

Endless number of settings
Seth Koenig, PhD, a staff scientist in the Herman Darrow Lab, recorded April’s brain activity during the selection process to help her care team keep track of which settings relieved her pain and to avoid causing a seizure. “We wanted to be sure she was really convinced the stimulation was helping her, and to calculate where to go next,” said Darrow. “We have an endless number of settings from which to choose as we build such an ultra-personalized model of stimulation.”

Three more days of working with April were devoted to tweaking the stimulation settings. The result? The team was able to bring her pain down from a self-assessed score of 8 out of 10 to zero. “April had been living with a chronic level of pain that made it difficult for her to perform normal daily functions,” said Netoff. “After stimulation, her whole outlook on life seemed to be transformed.”

Darrow then implanted her electrodes and the neurostimulator that would control them. He gave April an iPod so she could work with him to change the settings, if needed.

Improved cognition
One of the surprising things that Darrow and the team learned was that the stimulation improved April’s cognition, as shown by the excellent results she achieved on a challenging cognitive task. “We thought that if we stimulated using high frequency, which is what she preferred, the tradeoff would be a reduction in her cognitive performance,” Darrow said. “It turns out that it improved her performance. The fact that we could stimulate to reduce her pain and improve her cognitive performance at the same time is just wild.”

April is grateful for everything the U of M team did for her. “Going through the surgery and having someone continue to work with me was worth the two years of pain,” she said. “The first day I didn’t feel the pain as much, I knew that Dr. Darrow had saved me. Everyone in the world should know there is hope, it’s just a matter of advocating for yourself and getting to the right people like Dr. Benish and Dr. Darrow.”

To share what they learned from April, the Herman Darrow and Netoff Labs are preparing a case study about what they did for her. And if sometime in the future her brain develops enough plasticity to “reroute” its signals around the current stimulation settings and cause more pain, Darrow and April can find new settings to alleviate it – right from her living room couch.

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