Abstract
Objective To assess stiff person syndrome (SPS) misdiagnosis and identify factors differentiating SPS from non-SPS.
Background SPS is a heterogeneous immune-mediated central hyperexcitability disorder that is challenging to differentiate from alternative diagnoses.
Design/Methods Patients referred to the Mayo Autoimmune Neurology Clinic for SPS (01-Jul-2016 to 30-Jun-2021) were included. SPS diagnosis was defined as compatible clinical syndrome confirmed by an autoimmune neurologist and either serum positivity for high-titer GAD65-IgG (>20.0 nmol/L), glycine-receptor-IgG or amphiphysin-IgG (seropositive cases), or confirmatory electrodiagnostic studies (seronegative cases). Seven patients were excluded (diagnostic uncertainty). Patients were compared for clinical presentation, examination findings, laboratory and electrodiagnostic testing, and treatment responses.
Results Of 173 cases, 48 (28%) were diagnosed with SPS and 125 (72%) with non-SPS. Age and sex did not significantly differ in the two groups. Most SPS patients were seropositive (41/48 total: GAD65-IgG 27/41, glycine-receptor-IgG 12/41 and amphiphysin-IgG 2/41). Fibromyalgia/chronic pain syndrome or functional neurological disorder were the most common non-SPS diagnoses (81/125, 65%). True SPS patients more commonly had a history of exaggerated startle (81% vs 56%, p = 0.02), unexplained falls (76% vs 46%, p = 0.001) and prior autoimmunity (50% vs 27%, p = 0.005). On examination, SPS patients more often had hypertonia (60% vs 24%, p < 0.001), hyperreflexia (71% vs 43%, p = 0.001) and exaggerated lumbar lordosis (67% vs 9%, p < 0.001) but less likely had functional signs (6% vs 33%, p = 0.001). SPS patients more often had abnormal electrodiagnostic studies (74% vs 17%, p < 0.001), and at least moderate symptomatic improvement was more likely with benzodiazepines (51% vs 16%, p < 0.001) or immunotherapy (45% vs 13% p < 0.001). Seventy-one non-SPS patients received immunotherapy; only 4 had an autoimmune neurological condition.
Conclusions SPS misdiagnosis is common and most alternative diagnoses were non-neurologic. Misdiagnosis may be reduced by considering clinical and paraclinical factors; improved diagnostic accuracy will reduce exposure to unnecessary treatments and health care costs.
Footnotes
Disclosure: Dr. Chia has nothing to disclose. The institution of Dr. McKeon has received research support from Euroimmun AG. The institution of Dr. McKeon has received research support from National Institutes of Health. Dr. McKeon has received intellectual property interests from a discovery or technology relating to health care. Dr. McKeon has received intellectual property interests from a discovery or technology relating to health care. Dr. McKeon has received publishing royalties from a publication relating to health care. The institution of Dr. Flanagan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Flanagan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Flanagan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon Therapeutics. Dr. Flanagan has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Pharmacy times. The institution of Dr. Flanagan has received research support from Viela Bio. Dr. Flanagan has a non-compensated relationship as a Member of medical Advisory Board with The MOG Project that is relevant to AAN interests or activities. Dr. Flanagan has a non-compensated relationship as a Editorial board member with Journal of The Neurologic Sciences that is relevant to AAN interests or activities. Dr. Flanagan has a non-compensated relationship as a Editorial board member with Neuroimmunology Reports that is relevant to AAN interests or activities. The institution of Dr. Dubey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. The institution of Dr. Dubey has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Astellas. Dr. Dubey has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for AGRIMS. Dr. Dubey has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Advances in Neurology. Dr. Dubey has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Moffit Cancer Center. Dr. Dubey has received research support from Department of Defense. Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care. Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care. Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care. Dr. Zalewski has nothing to disclose. Dr. Pittock has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech, Inc. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sage Therapeutics, Inc. The institution of Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Astellas. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Prime Therapeutics. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche/Genentech. The institution of Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. The institution of Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MedImmune/Viela Bio. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB, Inc. Dr. Pittock has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Hoffman/LaRoche AG. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genetech. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for F. Hofman/LaRoche. The institution of Dr. Pittock has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. The institution of Dr. Pittock has received research support from Grifols. The institution of Dr. Pittock has received research support from NIH. The institution of Dr. Pittock has received research support from Viela Bio/MedImmune/Horizon. The institution of Dr. Pittock has received research support from Alexion Pharmaceuticals. The institution of Dr. Pittock has received research support from F. Hoffman/LaRoche/Genentech. Dr. Pittock has received intellectual property interests from a discovery or technology relating to health care. Dr. Pittock has received intellectual property interests from a discovery or technology relating to health care. The institution of Dr. Zekeridou has received research support from Roche/Genentech. Dr. Zekeridou has received intellectual property interests from a discovery or technology relating to health care. Dr. Zekeridou has received intellectual property interests from a discovery or technology relating to health care.
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