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When the body attacks the brain

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Dr. Andrew McKeon, one of two Mayo neurologists leading autoimmune neurology research, says autoimmune disorders can cause illnesses long believed to be untreatable mental illnesses.
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In the span of eight weeks, Dr. Denise Krivach, a former Abbott Northwestern radiologist, went from making retirement plans in the woods of Montana to being barely able to care for herself.

Doctors in Montana diagnosed her with dementia. But that didn’t seem right to her. When she arrived at Mayo Clinic in 2014, doctors ruled out dementia and Alzheimer’s disease.

"Alzheimer’s doesn’t run like that," said Dr. Andrew McKeon, a Mayo Clinic neurologist. "It runs over a matter of years or decades."

Krivach was diagnosed with neurological autoimmune encephalopathy. It is an underdiagnosed condition in which her own immune system was attacking her brain, causing nerve interference, swelling and a loss in cognition.

The diagnosis gave Krivach treatment options that not only stopped her cognitive decline but reversed it. Mayo Clinic is on the forefront of autoimmune neurology research — the study of immune disorders that affect the brain or nervous system. Leading researchers in the field are discovering new antibodies or protein anomalies in nerve cells that lead the immune system to attack or interfere with nerve function. Their work at Mayo Clinic offers hope to patients such as Krivach. A few years ago, she would have likely been resigned to permanent cognitive loss.

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Krivach’s condition was initially undiagnosed in part because the concept that the immune system can affect brain function is just now entering conventional medical understanding. The autoimm neurology field is going to get bigger, neurologists say.

Complex systems

The human immune system generates millions of types of antibodies that respond to specific targets. When functioning normally, those targets are potential diseases or invading cells. In a patient with a neurological autoimmune disorder, some antibodies mistake parts of cells at or around nerve cells for their intended targets. Those antibodies then mobilize the immune system to attack or interfere with nerve cells’ functions.

With millions of antibodies in the human immune system and billions of nerve cells in the human brain, the possible combinations for conflict are staggering.

"The complexity is huge," said Dr. Sean Pittock, a Mayo Clinic neurologist. "The field is really at an infancy stage."

Pittock and McKeon are leaders in the field at Mayo and worldwide. Pittock set up the nation’s first autoimmune neurology clinic at Mayo in 2006. He is director of the clinic’s Neuroimmunology Laboratory and the Center for MS and Autoimmune Neurology. Mayo neurologist Dr. Vanda Lennon, a pioneer in the field, opened the lab in 1981.

Mayo’s neurologists are at the forefront of research into how some cognitive and psychiatric disorders can be autoimmune-related. Until their work, conventional wisdom held that the brain was not affected by immune disorders.

"The concept that you could have a cognitive disorder that’s treatable — people rejected that because it’s degenerative," Pittock said.

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Certain cases and markers can lead to different diagnoses.

"If somebody develops epilepsy in their 30s, why is that?" Pittock asked. "Target the immune system, and you can cure that epilepsy."

Tests and treatment

The task to target the immune system is a complicated one. The immune system creates millions of different antibodies, each designed to recognize and combat specific targets. The daunting task for neurologists is to identify antibodies that can contribute to neurological problems under certain conditions. They’re just getting started.

"We’re not in the hundreds or thousands of antibodies — we’re in the 20s," Pittock said.

"We’re very committed to advancing the field," McKeon said.

With thousands of antibodies in a patient at any given time, researchers have a lot of noise to sort through to find which one is acting up. Fortunately, antibodies are singular in their task.

"Every single antibody has a specific target," Pittock said. "We’re very good at discovering antibodies that tell us something clinically."

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The researchers are also noting proteins or protein deficiencies that can appear in cells that trigger an immune response.

These discoveries have led researchers creating tests for some autoimmune disorders. Those did not exist when Pittock began his work at Mayo Clinic.

Pittock, McKeon and researchers at Mayo have developed a new way to detect specific antibodies. Doctors take a sample of the protein targeted by the as-yet unidentified antibodies, then place it into a cell that doesn’t express the target protein. The patient’s sample is introduced to the cell.

"So the protein is expressed the way they would be in a human being," Pittock said.

Piecing the puzzle

With tests available and the field growing, doctors are beginning to look at autoimmune causes of some long-known ailments. Patients presenting multiple sclerosis symptoms are now routinely tested for an autoimmune disorder that mimics multiple sclerosis.

A study in Olmsted County of incidences of encephalopathy shows that many cases are like Krivach’s — a neurological autoimmune disorder — and not caused by an infection. In 1995, the number of infectious encephalopathy cases was triple the number of suspected autoimmune neurology cases. The study showed this year the causes are nearly even. As more autoimmune tests are developed, McKeon and Pittock expect autoimmune-related cases to eclipse infectious cases.

Other cases are not so clear.

"Sometimes the patient has a combination of factors never seen before," said McKeon.

Other times, neurological autoimmune disorder symptoms can mimic something oddly specific. One disorder has symptoms that resemble strychnine poisoning, the neurologists said. Symptoms and illnesses caused by potential neurological autoimmune disorders can be broad. Antibodies can attack nerves of any organ or system.

"If you can imagine it, it can happen," Pittock said.

Researchers are also looking at correlations between some diseases and cancers in patients who later develop neurological autoimmune disorders.

Under diagnosed

Krivach is still recovering. When she first arrived at Mayo Clinic, she would have had difficulty living on her own, she said. Today, she lives a normal life but has some residual symptoms.

Wider understanding of neurological autoimmune disorders will mean a quicker diagnosis and a better prognosis. However, recovery can vary between patients, doctors said.

Pittock compared it to recovery of an injured knee that might or might not develop arthritis.

"It’s kind of similar in the brain — you get the attack, you get the hit," Pittock said. "The patient can still have problems, but there’s no inflammation."

Krivach continues to improve.

"I hope I will be able to go back and spend some time in nature," she said.

Krivach added she’s grateful to McKeon, Pittock and the autoimmune neurology team. In a new field, there is still a large element of deduction and hypothesizing.

"To diagnose and treat and manage the way they do here, there is an art involved," she said.

Related Topics: MAYO CLINIC
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