Complexities With Management and Treatment of Neuroimmune Disorders

WATCH TIME: 6 minutes

Rare neuroimmune disorders are immune-mediated disorders of the central nervous system in which cells become “confused” and mistakenly attack an organ within a person. Patients may have acute flaccid myelitis (AFM) or transverse myelitis (TM) when the spinal cord is affected or optic neuritis when the optic nerve is impacted. In acute disseminated encephalomyelitis (ADEM), MOG antibody disease (MOGAD), and neuromyelitis optica spectrum disorder (NMOSD), there are various patterns of organ involvement, and in some disorders there is the potential for recurrent events.

Over the years, the detection of these disorders, and the way they are treated, has improved significantly. For years, neuromyelitis optica was thought to be a variant of multiple sclerosis (MS), but in 2004, a circulating immunoglobulin autoantibody was reported in patients with neuromyeltis optica that was absent in those with MS. Within a year, the astrocyte water channel protein aquaporin-4 was identified as its target, leading to several advanced therapeutics more than a decade later.

In collaboration with the Siegel Rare Neuroimmune Association, NeurologyLive^® hosted a Roundtable Discussion focusing in on the major advances since the organization’s birth, nearly 30 years ago. The panel included Sanford Siegel, current president of SRNA, Benjamin Greenberg, MD, vice chair of clinical & translational research at UT Southwestern Medical Center, and Douglas Kerr, MD, chief medical officer of GeneratioBio and a key figure in the establishment of the Johns Hopkins Transverse Myelitis Center, the only such specialized center in the world. In this episode, the panel reviewed the challenges of identifying patients with neuroimmune disorders early and ensuring quick and effective treatments are implemented. Furthermore, they discussed how research has shaped treatment decisions and improved outcomes and quality of life for patients.

Marco Meglio: Let's now explore the complexities involved in treating and managing these disorders.

Benjamin Greenberg, MD: Beyond the acute phase, we still face challenges in determining the best rehabilitation strategies. Conducting randomized trials in this area remains difficult, and it's uncertain if we'll ever have enough data. Consequently, many patients, depending on local resources, may not receive adequate rehabilitation. There hasn't been enough emphasis, particularly outside a small community, on the significant functional benefits achievable through early, aggressive, and long-term rehabilitation. This is a low-hanging fruit for the community, where we don't have to wait for a new stem cell or drug; the techniques are there, but we need to implement them systematically.

Another aspect we should consider is restorative therapies to regain function in those with lasting deficits. However, I want to mention that, historically, the neurology field hasn't been very hands-on with rehabilitation. We've tended to focus on writing prescriptions and not being directly involved in the rehabilitation process.

Douglas Kerr, MD: Absolutely, Ben. In the acute phase, we recognize the intense immune response with high cytokine levels and autoantibodies. We understood that halting this inflammation as quickly as possible was crucial, akin to managing an acute myocardial infarction. Thus, we leaned towards aggressive therapies like therapeutic plasma exchange, cyclophosphamide, Rituxan, and high-dose steroids to curtail the inflammation and salvage affected tissue.

However, once inflammation subsides, there was a prevailing belief, when I entered the field, that what you gain within the first six months post-spinal cord injury is all you'll ever regain. We now know that this notion is unequivocally false. Ongoing rehabilitation, including novel approaches like functional electrical stimulation bikes, can stimulate neural plasticity for years after the initial injury. While conducting randomized studies in this area is challenging, we've witnessed remarkable progress. Several generations of physicians have adopted this ethos of aggressive care, managing inflammation, supporting patients and families, and advocating continued rehabilitation because we believe in the potential for ongoing improvement.

Sanford Siegel: I'd like to add a milestone in our efforts. We recognized that while academic centers were training physicians in rare neuroimmune disorders, the pace wasn't fast enough. Many regions lacked specialists in these disorders, including major cities and states like Florida. In 2008, we introduced the Jim Lubin Fellowship, named in honor of one of our association's original officers. Through this fellowship, we accelerated the training of clinicians and researchers in these disorders. Centers like Ben's were identified as suitable training sites due to their experience in treating a significant number of patients over a two-year period. This initiative has made a difference in training more physicians and researchers in the field. Even beyond the fellowship, other centers continue to train professionals, fostering a collaborative community where experiences and insights are shared to benefit patients.