Neuroimmunological Disorders: Some Rare and Some Controversial
Wendy S. Vargas, MD, an Assistant Professor in Neurology at Columbia University Medical Center, is pioneering an uncommon path. She specializes in the treatment of children and adults with neuroimmunologic disorders, which constitute an array of different diseases, some quite rare-even controversial-and many of which occur infrequently in children.
"I see children and adults who have immune-mediated disorders of the central nervous system, so I see things such as multiple sclerosis [MS], neuromyelitis optica, optic neuritis, transverse myelitis, anti-N-methyl-D-aspartate receptor encephalitis-pretty much any neurologic disorder that has an immune basis to it," said Dr. Vargas, a pediatric neurologist at NewYork-Presbyterian/Morgan Stanley Children's Hospital.
"I'm a child neurologist who then chose to subspecialize in an 'adult' subspecialty," she added. "I feel comfortable seeing both children and adults as a child neurologist, and I think that's rare." What also is rare is the characterization of these disorders in children, an area of research in which Dr. Vargas has chosen to specialize.
In Search of Antibodies
"Many children have neuroimmunological disorders-I think that they just haven't been described yet," she said. "I'm definitely seeing more cases than I expected to see when I decided to specialize in this."
Even something like epilepsy, a common childhood neurologic disorder, may have an as yet unappreciated immunologic basis. For example, for some children with difficult-to-treat seizures that do not respond to typical antiepileptics, treatment with steroids or intravenous immunoglobulin, which are typically used to treat diseases with an autoimmune component, can be effective, Dr. Vargas said.
"I think that a lot of neurologic disorders are probably immune mediated. We just haven't found the antibody yet."
Most of Dr. Vargas' current research is focused on MS in children.
"If you look at MS in general, it is rare in children," she noted. When it does occur in children, for the most part, it is not associated with the same degree of physical disability typically observed in adults. Rather, the disability in children with MS tends to be cognitive. Dr. Vargas has received funding from the National MS Society to further evaluate the presentation of cognitive difficulties in children with MS.
"My hypothesis is that children with early MS can have cognitive dysfunction that can affect their ability to perform in school, and we're trying to correlate that with areas of atrophy in the brain."
Work in this area, published by Dr. Vargas and her colleagues at Weill Cornell Medicine, correlates abnormalities in white matter with atrophy in connecting gray matter and processing speed in patients with early MS (Am J Neuroradiol 2015;36:702-709).
In Search of PANDAS
Dr. Vargas also is venturing into a new area of neuroimmunologic research, and this one is surrounded by controversy. She will be looking at PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections), a group of rare neurologic disorders with onset that occurs after infection with Streptococcus.
"This is a controversial topic because no one has proven that Streptococcus infection actually causes what we see in these children," Dr. Vargas said, which is the development of tics or symptoms of obsessive-compulsive disorder with sudden onset and severe.
So far, she said, the existence of PANDAS is solely based on the presence of physical symptoms in children with a recent streptococcal infection, as a specific pathology has yet to be defined.
"I've never seen a more controversial topic-many physicians don't believe that it exists," she said.
Dr. Vargas' colleague, Dritan Agalliu, PhD, an Assistant Professor of Pathology and Cell Biology at Columbia University Medical Center, has developed a mouse model demonstrating that inoculation of mice with Streptococcus can trigger the migration of Streptococcus-specific Th17 cells to the brain, the formation of autoantibodies that target the central nervous system and the development of PANDAS-like symptoms (J Clin Invest 2016;126:303-317; Future Neurol 2016;11:63-76).
"Now that he has found that antibody in the mice, we're looking to see if we can find it in children who have this disorder."
Dr. Vargas will be collaborating on the project with Susan E. Swedo, MD, who, along with her team at the National Institute of Mental Health, was the first to describe PANDAS. Dr. Vargas' group is currently awaiting institutional review board approval, and she hopes to begin seeing patients and collecting blood and saliva samples for evaluation within the next couple of months.
"Proving the pathogenesis and proving that this is actually a disorder that has an immune basis-I think that is very exciting."
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