November 10-15

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ACR Convergence 2023

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New data changes diagnosis, treatment of CNS vasculopathies, antibody-associated syndromes


4 minutes

A growing body of observational clinical evidence is changing the way rheumatologists classify, diagnose, and treat vasculitis and antibody-associated syndromes in the central nervous system (CNS). In some cases, specific diagnostic testing has been developed in recent years. In other diseases, growing awareness is leading to more precise diagnosis and treatment.

Tracey Cho, MD

“The discovery of antibody-mediated neurologic diseases, in particular diseases that are driven by immune response as opposed to degenerative or infectious disease, has opened both new diagnostic and therapeutic potential,” said Tracey Cho, MD, Co-Director of the Autoimmune and Infectious Neurology Program at Massachusetts General Hospital. “We now know of antibody-mediated diseases that did not have an explanation and were probably misdiagnosed previously in many cases and not appropriately treated.”

Dr. Cho will explore the complex world of primary central nervous system vasculitis during a clinical symposium on Central Nervous System Vasculopathies and Antibody-Associated Syndromes from 4:30 – 6:00 pm on Monday in Salon B. Primary CNS vasculitis is similar to how vasculitis affects the kidneys or lungs, but more difficult to diagnose and potentially more devastating. He will focus on multiple diseases that can mimic CNS vasculitis but may not be caused by inflammation and need very different treatment.

“The immunomodulatory therapies we have in our arsenal are growing but remain either very expensive or have their own side effect potential,” he said. “You don’t want to commit to these therapies without some level of certainty of the diagnosis of primary CNS vasculitis.”

Many of the vasculopathies that affect kidneys or lungs can also affect the brain, Dr. Cho said. Primary CNS vasculitis involves only the brain. CNS-only involvement is a useful diagnostic marker but also cause for significant concern.
Kidney and lung tissue affected by vasculitis has good potential to regenerate. And both organs can still function adequately if a small portion has been injured.

“If you have damage to the brain, depending on the precise location of the injury, it could immediately and drastically impair patient functioning,” he said. “And the brain has limited potential to regenerate.”

Primary CNS vasculitis can be confirmed by tissue biopsy, but obtaining a sample from the brain is significantly more complicated than from most other organs. One of the primary CNS vasculitis mimics is a genetic disease that can be directly identified from skin samples or by way of genetic screening of serum samples. Similar noninvasive testing for primary CNS vasculitis is still in development.

Neuromyelitis optica spectrum disorder (NMOSD) is another inflammatory disease of the CNS that has traditionally been underdiagnosed and treated inappropriately. The recent discovery that NMOSD is strongly associated with AQP4-IgG, a circulating autoantibody to the water channel aquaporin-4, is changing both diagnosis and treatment.

NMOSD causes inflammatory injury to the optic nerves, spinal cord, and to a lesser extent, other CNS regions. About 75 percent of patients with NMOSD have detectable serum AQP4-IgG. Up to half of affected individuals have other positive autoantibody tests (such as ANA or ENA), and about one-third will have at least one co-existing autoimmune disease.

Dean M. Wingerchuk, MD

The NMOSD clinical phenotype may occur in the context of lupus or SjÖgren’s disease, said Dean M. Wingerchuk, MD, Professor of Neurology at Mayo Clinic Arizona. Such patients should be tested for aquaporin-4 antibodies.

“Central nervous system presentations can dominate the picture with spinal cord or optic nerve or other CNS involvement,” Dr. Wingerchuk said. “Typical findings for either serology or clinical evidence, or both, suggesting lupus or Sjogren’s may not be the full answer, or even the right answer. There is now good data to show that these AQP4-IgG seropositive patients actually have NMOSD and co-existing, rather than causative, rheumatologic disease.”

There are no agents approved to treat NMOSD, he said. That is likely to change in light of intensive research into mechanisms of AQP4-IgG autoimmunity and therapeutic targets that can interfere with those mechanisms.

There are three clinical trials underway that could result in approved indications, but for now, the treatment of choice is suppression of antibody production. The most commonly used agent in North America is rituximab, but clinical experience suggests that azathioprine and mycophenolate also can provide positive results.

“This symposium is a rare opportunity to hear from neurologists who also have great familiarity with the rheumatologic aspects of these immune-mediated diseases,” Dr. Cho said. “None of us are rheumatologists, but we have frequent interactions with rheumatologists and a particular expertise with the nervous system aspects of rheumatologic disease.”

Central Nervous System Vasculopathies and Antibody-Associated Syndromes
4:30 – 6:00 pm Monday • Salon B