One in a Million: A Rare Case of Stiff Person Syndrome and its Diagnostic Challenges
Background:
Stiff person syndrome (SPS) is a rare autoimmune disorder characterized by progressive muscle spasms and rigidity, commonly associated with high titers of anti–glutamic acid decarboxylase 65 (anti-GAD65) antibodies. Diagnostic challenges often arise due to similar symptomatology to more common conditions and lack of a formally accepted diagnostic criteria, leading to a mis- or late diagnosis.
Design/Methods:
A 58-year-old marathon-runner with recently diagnosed type-1 diabetes mellitus (T1DM) presented with a 4-year history of unsteadiness, decreased exercise tolerance, diffuse joint pain, neuropathic pain, hoarse voice, difficulty reading and progressive gait impairment. For the first three years, he was seen by three neurologists, remained undiagnosed and was symptomatically treated with duloxetine, bupropion, lamotrigine, gabapentin, baclofen, meloxicam, modafinil, and dextroamphetamine with minimal to no improvement in his symptoms. Patient’s endocrinologist had ordered serum anti-GAD65 antibodies which were slightly positive (51.4IU/mL) when he was initially diagnosed with T1DM which raised suspicion for SPS. Electromyography showed continuous motor unit activity in agonist and antagonist muscles. On 12/2024, patient presented to the emergency department after a fall caused by worsening spasms and gait impairment. Neurological exam was significant for spasmodic dysphonia, abnormal saccades, increased tone with stiffness in all extremities, sensory changes in a glove and stocking distribution, stooped posture, and wide-based robotic gait. Repeat serum anti-GAD65 was 44.1IU/mL and CSF was negative for oligoclonal bands, anti-GAD65, anti-amphiphysin, anti-DPPX, and anti-glycine antibodies.
Results:
Given the high clinical suspicion of SPS, intravenous immunoglobulin (IVIG) therapy was initiated. He had a dramatic response after the first dose, with significant improvement in his dysphonia, gait, tone and spasm frequency.
Conclusions:
Approximately 80-98% of patients with SPS are seropositive for anti-GAD65, typically at high titers (usually >10,000IU/ml), of which over 85% have intrathecal antibodies. This case study highlights the diagnostic challenge of SPS, particularly in patients with overlapping symptoms and low antibody titers.
Disclaimer: Abstracts were not reviewed by Neurology® and do not reflect the views of Neurology® editors or staff.