As an undergraduate history major at Princeton, Jeffrey Gelfand, MD, wrote his thesis about the death of Captain James Cook on his third voyage around the world. It is this same attraction to unraveling the mystery behind the unknown — and persevering — that has encouraged his research work in neuroimmunology as a 2011 AAN Clinical Research Fellow.
Dr. Gelfand graduated from Harvard Medical School in 2006, and completed his neurology residency at the University of California, San Francisco (UCSF) in 2010. Now a clinical instructor and research fellow at the UCSF Multiple Sclerosis Center and San Francisco General Hospital department of neurology, Dr. Gelfand hopes to use his fellowship to discover new markers to distinguish neurosarcoidosis from other causes of CNS inflammation.
WHAT DO YOU HOPE TO FIND OUT?
We want to identify novel phenotypic markers of sarcoidosis in the central nervous system — to improve diagnosis and discover better ways to distinguish sarcoidosis from other causes of CNS inflammation. We also hope to broaden our understanding of the pathogenesis of sarcoidosis in the CNS.
Because sarcoidosis affects the lungs in most patients at some point in the disease course, I am also collaborating with investigators in pulmonology through the UCSF Sarcoidosis Research Program. We will be studying patients with neurosarcoidosis, as well as prospectively evaluating patients with sarcoidosis in other organ systems to look for evidence of neurological involvement and comparing phenotypic markers between patients with neurosarcoidosis and sarcoidosis in other organs. We will also analyze how phenotypic abnormalities differ between patients with neurosarcoidosis and multiple sclerosis.
WHAT IS YOUR PROPOSED METHODOLOGY?
We plan to look for inflammatory distinguishing “signatures” in the eye using non-invasive retinal imaging, in the brain using high resolution MRI, and in the blood and spinal fluid using high-throughput techniques. This may also help to inform us about the underlying biology of sarcoidosis and how different types of inflammation affect the nervous system.
WHY DID YOU CHOOSE TO STUDY SARCOIDOSIS?
Sarcoidosis is an inflammatory disease of unclear origin that is characterized by non-caseating granulomatous inflammation. About 5 to 10 percent of patients with sarcoidosis have neurological involvement, which can be severe and cause permanent disability. Short of an invasive biopsy, there is no reliable test to diagnose neurosarcoidosis or distinguish sarcoidosis from other causes of CNS inflammation.
Sarcoidosis is commonly considered as a diagnosis when patients have inflammatory neurological syndromes, yet because of the lack of reliable non–invasive testing, neurosarcoidosis remains one of the most challenging diagnoses to make in neurological practice.
WHO INSPIRED YOUR INTEREST IN THE RESEARCH QUESTION?
When I was a first-year neurology resident rotating through Dr. Stephen Hauser's clinic in the MS Center [at UCSF], I evaluated a young woman with steroid refractory neurosarcoidosis affecting the brain and spinal cord. Her diagnosis had taken over two years — in part because there was no systemic evidence of sarcoidosis at the time when her neurological syndrome presented. It was only later that she developed skin and lung involvement. With Dr. Hauser's mentorship and guidance, I was able to care for her longitudinally as we worked through the challenges of optimizing treatment and managing symptoms. This experience inspired my interest in studying neurosarcoidosis.
During my residency, I also helped to take care of a number of patients with sarcoidosis who had been treated for other conditions before a correct diagnosis was made. I also worked with patients who were initially diagnosed with sarcoidosis but turned out to have other pathologies. These experiences made me realize how difficult it is to diagnose neurosarcoidosis and I came to appreciate the dearth of evidence available to guide treatment.
WHO ARE YOUR RESEARCH MENTORS?
Dr. Ari J. Green in the UCSF Multiple Sclerosis Center has made a huge impact on my career through thoughtful and dedicated mentorship. He inspired me to pursue neuroimmunology and patient-oriented clinical research. Dr. Stephen Hauser has also been a wonderful mentor. He motivated me to pursue neuroimmunology and to ask meaningful, patient-oriented questions. Dr. Richard Price at San Francisco General Hospital has also been an influential mentor by broadening my conception of CNS inflammation to include inflammatory responses to infection and helping to imagine ways of improving how we distinguish different types of CNS inflammation from one another.
WHY DID YOU FOCUS ON NEUROIMMUNOLOGY?
Neuroimmunology is one of the most exciting areas in neurology. We are just beginning to understand the intricate ways in which inflammation can affect neurological functioning, most notably in primary inflammatory diseases of the nervous system, but also in less direct ways, as in the emerging evidence of inflammatory mediators in the pathogenesis of neurodegenerative disease.
AAN Clinical Research Training Fellowships are funded by the AAN, the AAN Foundation, and the AAN Foundation Corporate Roundtable, and provide $55,000 per year for two years, plus $10,000 per year for tuition to support formal education in clinical research methodology at the fellow's institution or elsewhere. Fourteen fellowships were awarded for 2011, and more than 70 training fellowships have been awarded through the program since its inception in 1996. For more information about the program, visit http://bit.ly/egrG8L.
To learn more about the UCSF Sarcoidosis Research Program, visit sarcoidosis.ucsf.edu/.