Late-onset stiff-person syndrome: challenges in diagnosis and management

Abstract

Background: Stiff person syndrome (SPS) is a rare slowly progressive autoimmune neuronal hyperexcitability disease with very-high GAD-65 antibody titers that most commonly presents above the age of 20, with muscle stiffness, painful muscle spasms, slow gait, and falls leading to disability. In other autoimmune disorders, late-onset disease has different symptom-spectrum and outcomes, but there is no information regarding late-onset SPS (LOSPS). Objective: Highlight delayed diagnosis and poor tolerance or incomplete response to therapies of patients with LOSPS and outline how best to increase disease awareness early at onset. Design: A retrospective chart review.Methods: We reviewed GAD-positive SPS patients with symptom onset above age 60, identified among 54 SPS patients, examined, treated and followed-up by the same clinicians, focused on clinical presentation, misdiagnoses, response and tolerance to therapies, and evolved disability. Results: Nine patients had LOSPS with symptom onset at median age of 61 years (range 60–78), and current median age of 73. The median time from symptom onset to SPS diagnosis was 3 years; prior to diagnosis, five patients were treated for lumbosacral radiculopathies (one with laminectomy), two for Parkinson’s disease, one for multiple sclerosis, and another for cerebellar degeneration. Progressive decline occurred rapidly in all patients; at time of diagnosis, six patients were already using a cane or walker and two were wheelchair-bound. Tolerance and response to treatment were limited; two patients did not respond to IVIg, two discontinued IVIg despite early response due to comorbidities (cardiac disease, thrombosis), four others partially responded to IVIg and one to rituximab; several could not tolerate high doses of oral antispasmodics due to somnolence; and two patients died. Conclusions: LOSPS is almost always misdiagnosed for other similar conditions commonly seen in the elderly. Patients with LOSPS decline quickly to clinically severe disease due to delayed treatment initiation, poor response or tolerance, other comorbidities, and possibly immunosenescence. Increased awareness that SPS can occur in the elderly mimicking other disorders is important for early diagnosis and treatment, even necessitating earlier immunotherapy initiation, compared to their younger counterparts, to prevent faster-evolving severe disability.