When, in 2022, singer and international celebrity Celine Dion announced what she called her “one-in-a-million diagnosis” of stiff person syndrome, clinicians and medical scientists who specialize in the disorder took a deep breath. Scott D. Newsome, DO, professor of neurology and director of the Johns Hopkins Stiff Person Syndrome Center, Baltimore – a glass-half-full kind of person – saw in Ms. Dion’s worrying announcement a huge opportunity nonetheless: To raise awareness about the rare cluster of disorders known collectively as stiff person spectrum disorders (SPSD).
“Even at the clinician level, if you don’t know the hallmark signs and symptoms, you could possibly misdiagnose it,” Dr. Newsome said in an interview.
Dr. Scott D. Newsome
But misdiagnosis can go either way; increased awareness of SPSD can have a downside. Thirty years ago, when Marinos C. Dalakas, MD, first began studying SPSD, the diagnosis was frequently missed – “because people were not aware of it,” he said. But now, Dr. Dalakas, professor of neurology and director of the division of neuromuscular diseases in the department of neurology at Thomas Jefferson University and the Jefferson Hospital for Neuroscience, both in Philadelphia, said overdiagnosis is also a concern, particularly with increased public awareness.
“Just this last month I saw two patients who told me: ‘I read about it, and I believe I have symptoms of stiff person,’ ” he said.
These days, most patients in whom SPSD is suspected end up with an alternate diagnosis. In a recent retrospective study that Dr. Dalakas coauthored, of 173 patients who had been referred to the Mayo Clinic in Rochester, Minn., with suspected SPSD,1 Dr. Dalakas and colleagues determined that only 48 (27.7%) actually had the disorder – meaning that the rest might have been unnecessarily exposed to immunosuppressive SPSD therapies and that treatment for their actual disorder (most often, a functional neurologic disorder or nonneurologic condition) was delayed.
At the root of both underdiagnosis and overdiagnosis of SPSD is the heterogeneity of the condition and a lack of definitive diagnostic markers.
SPSD has been considered an autoimmune disorder for a long time, and observations by Dr. Dalakas and others have shown that as many as 35% of cases co-occur with another autoimmune disease, such as vitiligo, celiac disease, rheumatologic disease, type 1 diabetes mellitus, and thyroid disease (Grave’s disease and Hashimoto’s thyroiditis).2 A more recent study by his group observed an even higher rate (42%) of comorbid autoimmunity, with autoimmune thyroid disease being most common. However, although most cases of SPDS are characterized by an elevated level of glutamic acid decarboxylase (GAD)65-IgG, these autoantibodies are not specific to SPSD (low levels are also seen in diabetes, thyroid disease, healthy controls, etc.). Some SPSD patients have less common autoantibodies and a minority has no autoantibodies. Dr. Newsome said seronegative cases and the antibody presence and titers not being associated with disease severity or treatment response are clues that “SPSD does not appear to be a primary antibody-mediated condition and that there must be other immune factors at play.”