Does autonomic dysreflexia affect our immune system response? As anybody with a spinal cord injury should be aware, AD — an overactive nervous system response to pain or discomfort below the SCI level — causes a sudden spike in dangerously high blood pressure that must be immediately addressed. AD affects people with SCI levels above T6 and in rare cases as low as T8. It can be a medical emergency that, left unchecked, can cause stroke, seizure, organ damage or even death.
According to a recent study done at Ohio State University’s Wexner Medical Center, AD damages the immune system of mice. Titled “Autonomic Dysreflexia Causes Chronic Immune Suppression After Spinal Cord Injury,” the study says that people with high-level SCI have weakened immune systems that leave them more susceptible to infections, which can lead to an untimely death. The study showed that AD plays a part in immune suppression of mice. On the hopeful side, researchers found drug compounds that mitigate immune suppression caused by AD.
In the study, researchers created SCI in two groups of mice at T3 and T9 respectively, then added a “stimulus” consisting of a specific amount of overfilling of the bowel and “pinching” of the skin near the hip. The stimulus triggered AD in the mice with T3 SCI. Researchers also found that each bout of AD caused a release of hormones called catecholamines — specifically adrenaline and noradrenaline — part of the body’s “fight-or-flight response” that causes an increase in heart rate, blood pressure and blood glucose levels. This increase kills immature white blood cells, the cells that fight infection, and results in immune suppression.
Repeated, frequent bouts of AD caused extensive damage to the immune systems of the mice and created a disorder called “central nervous system injury-induced immune deficiency syndrome.” The immune systems of the mice were so damaged that they were open to recurrent or chronic life-threatening infections, and they also had poor immune response to vaccines.
The mice that had SCI at T9 did not develop AD, and while their overall immune response was mildly depressed, the study reports the effect was “nonsignificant.”
The good news: During the study, researchers found a way to mitigate the immune damage caused from AD by injecting mice with compounds that act as blocking agents. This prevents the catecholamines from attaching to white blood cells. Repeated injections of the compounds restored immune function, suggesting that further research could eventually lead to the development of a drug that would prevent immune system damage from AD and restore immune function in people with SCI.
Meet the Researcher
One of the researchers in the study, Mark S. Nash, Ph.D., a professor and principal investigator at The Miami Project to Cure Paralysis, has been studying immune suppression in people with SCI for the past 14 years. He says that earlier studies support the growing body of evidence that people with SCI above T6 have higher rates of immune suppression and are more susceptible to infection than people with SCI at levels below T6. The big question has been, why? “Consensus used to be that it was all due to neurological mechanics of SCI, things like bladder management, reduced respiratory control, and skin breakdown,” he says. However, Nash and others believed there was more to it.
The idea for the study came about in part because immune suppression in nondisabled people is well associated with stress or stressors, says Nash. He and other researchers started thinking about AD as a big-time stressor, which led to the Ohio State study.
T6 is a critical level in terms of AD because the nerves between T6 and T9 control the adrenal glands, where catecholamines come from. With SCIs at or above T6, says Nash, control of the adrenal glands is no longer connected to the brain, so they act reflexively to stimulus, such as a full bladder, full bowel, skin pressure or any type of pain below the level of injury. AD doesn’t happen in lower SCI levels because the brain can control and moderate the release of catecholamines when there is some type of pain or stimulus.
The study also included monitoring changes in a human subject during a bout of AD. A volunteer with C5 quadriplegia underwent a mild episode of AD caused by letting his bladder overfill. This caused an elevation of his blood pressure and release of catecholamines. “His immune system went haywire for a couple of hours after the AD episode,” says Nash. “People with SCI above T6 generally have episodes of AD four to six times a day, commonly due to stimulus from dealing with bowel and bladder issues.”
Stress appears to be the culprit that AD creates. Nash says that in people with SCI, the effects of AD can be similar to stress experienced by nondisabled people when they over-exercise. “We know that after people run marathons, they have high levels of long-lasting catecholamines in their systems, and marathon runners have high rates of upper respiratory infections,” he says. “A colleague who looked at the stress AD puts on a person’s system remarked to me, ‘So it’s like they are running four to six marathons a day, that’s a lot of stress!’”
Like many aspects of SCI, immune suppression in relation to SCI is complicated, including how prevalent it is. Although a PubMed search on immune suppression and chronic SCI didn’t come up with many results, this is likely to change as life expectancy with SCI continues to grow. According to a 2009 University of Washington study, in the 1940s people with SCI only lived, on average, 18 months post-injury. As of 1998, life expectancy of quadriplegics had risen to 70 percent of the general population, and for paraplegics it is up to 86 percent. We are living longer, and the Ohio study is timely. Especially because there are varying experiences on SCI and immune suppression.
Not Everyone Agrees
Dr. Diana Cardenas, chair of the department of Physical Medicine and Rehabilitation at University of Miami Miller School of Medicine, says that clinically, she doesn’t see much immunosuppression in patients with SCI. What she does see are lots of UTIs, bowel management problems, and pressure ulcers, as well as respiratory complications in quadriplegics. She says that infections and complications related to infection are a result of mechanics — the result of vulnerability due to the loss of normal neurologic innervation with SCI — and the people she sees with these infections respond to the usual treatments.
“I haven’t seen good evidence that there is suppression of the immune system simply because of a spinal cord injury,” says Kathleen Dunn, a clinical nurse specialist and rehab case manager.
Dunn’s clinical experience in chronic SCI and immune suppression is similar to Cardenas. People with chronic SCI are more vulnerable to infection because of mechanical issues. Neurogenic bladder leads to UTIs, reduced sensation and muscle mass leads to pressure ulcers, and higher level SCIs lack respiratory muscles that enable a full, deep cough. All of these things can be associated with infections, explains Dunn.
When it comes to cervical level injuries, New Mobility has prematurely lost quite a few friends where immune suppression may have played a part. However, although some with SCI succumb to infection all-too early, Dunn points out that she sees people in her clinic who are 20-50 years post-injury. A quick visit to the Quad-List Discussion Group shows there are quads celebrating 45 years post-injury.
If this seems confusing, it’s because there are no clear-cut answers. The discussion at the end of the Ohio study states that although AD is prevalent after high-level SCI, not everyone with high level SCI and AD gets serious infections or responds poorly to vaccines. Unlike lab mice, people with SCI have different lifestyles and genetics. Some do better than others in terms of exercise, attention to diet, bladder, bowel, and skin care. Everything plays a role.
Kim Anderson-Erisman, Ph.D., a researcher and director of education for The Miami Project to Cure Paralysis, and also a quad, explains that part of what seems like a disconnect is that health care providers are not necessarily looking for immunosuppression. They are looking for a way to cure the problem, and the cure may be antibiotics, teaching better bladder or bowel care, instruction on how to do a mirror-skin check or prescribing a better seating system — so they wouldn’t generally wouldn’t run lab tests to look for immunosuppression.
“We do know something happens when people pass over the 20-plus year post-injury mark. At some point things that were fine for years start going wrong,” says Erisman. “In people, we don’t know what the ‘something’ is yet.” In the animal research Nash worked on, immunosuppression in chronic injuries is absolutely evident. “The takeaway for me is that we do not know enough about how SCI affects the immune system chronically, and we do not know enough about repetitive daily bouts of mild or silent AD. We need more research on both of these and how they interact.”
The Takeaways: What to Do
Nash found similar patterns in his research. Immune suppression appears to be a piece of the puzzle that is growing in importance in regard to why people with SCI are able to fight off infections such as pneumonia, UTI or infections from skin breakdown in earlier post-injury years, but when you go further out, 20-30 years or more, they succumb to the same infections, he says.
There are several goals of the Ohio State study, according to Nash. The first one is to draw attention to the significance of AD and the part it plays in infection susceptibility. “The study confirmed that AD is much more serious than we thought. It is much more than just an annoying symptom.”
The second takeaway from the study, Nash says, is that people who get AD often can’t tell how serious these episodes are. When the subject in the Ohio State study underwent an AD episode, he thought the symptoms were pretty mild — the researchers didn’t drive him to a crisis headache — and yet even with this mild bout of AD, there was a substantial change in his autonomic function. But these changes may not be very perceptible to people with SCI.
For readers, the takeaway should be that AD is very serious, and it’s important to do what you can to keep bouts to a minimum. Trying to manage AD is akin to detective work. You often have to eliminate certain potential causes to arrive at the actual cause.
Dunn advises focusing on things you can control. Take proper care of your bladder — empty on a regular basis and don’t let it overfill. Work with your urologist and get checked for bladder and kidney stones. Do weight shifts to keep your skin intact, and check pressure spots with a mirror. Stay on a regular bowel routine.
Also, work hard to stay healthy. Eat right and try and stay at the proper weight. Dunn advises talking with your doctor about getting an annual flu vaccine and also a pneumovax. Dunn says at the VA they give the pneumovax to new SCIs at T12 and above and recommend they get it again when they turn 60. “I pretty much consider somebody has an impaired cough all the way down to T12,” she says. “Even at T10 or T11, a person doesn’t have all the lower abdominal muscles needed for a full, robust cough,” she says. Finally, if you have a higher level of injury, be sure to understand how to have somebody help you cough.
• Autonomic Dysreflexia Causes Chronic Immune Suppression After Spinal Cord Injury, www.ncbi.nlm.nih.gov/pmc/articles/PMC3735880/
• Autonomic Dysreflexia Education Module, courtesy of Craig Hospital, www.craighospital.org/repository/documents/HeathInfo/PDFs/765.AutonomicDysreflexia.pdf
• Bladder Management for Adults With Spinal Cord Injury, www.craighospital.org/repository/documents/HeathInfo/PDFs/310.CPGBladderManagementafterSCIforHealthcareProviders.pdf
• Bowel Problems, www.craighospital.org/repository/documents/HeathInfo/PDFs/706.Bowel.Problems.NOD.pdf
• Preventing Pressure Sores, www.craighospital.org/repository/documents/HeathInfo/PDFs/322.ModelSystem-PreventingPressureSores.pdf
• Quad-List Discussion Group, www.makoa.org/quadlist.htm