Surgeons remove thymoma and a woman’s stiff-person syndrome improves

A 60-year-old woman whose painful muscle spasms left her unable to walk regained independent movement after surgeons removed a small tumor from her thymus, according to a case report published in General Thoracic and Cardiovascular Surgery Cases. Two years after the operation, she could walk without assistance, climb stairs unaided, and had stopped taking diazepam, the muscle-relaxing medication she had needed since her diagnosis. The tumor turned out to be a WHO type B1 thymoma, and her neurological decline traced back to stiff-person syndrome, a rare autoimmune disorder in which the body’s own antibodies sabotage the brain’s main braking system for muscle activity.

Stiff-person syndrome, first described by Moersch and Woltman in 1956 as stiff-man syndrome, affects roughly one person per million, with a female predominance and typical onset between 30 and 60 years of age. The disorder is characterized by progressive muscle stiffness and painful spasms that predominantly involve the axial muscles, producing the gait disturbances that brought this patient to neurologists. In about 5% of cases the syndrome is paraneoplastic, meaning it is triggered by a cancer elsewhere in the body, most often breast cancer. An association with thymoma, a tumor of the thymus gland, is rare, which is what makes this documented recovery noteworthy for clinicians weighing surgery against continued drug therapy.

The patient’s troubles began innocuously. With no significant medical or family history, she noticed discomfort in the sole of her right foot during yoga practice, followed by progressive rigidity of the right ankle. Two weeks later, painful muscle stiffness developed in both lower extremities, leaving her unable to stand or walk. Admission to the neurology department revealed bilateral spasticity, worse on the right side, hyperactive deep tendon reflexes, and a positive Babinski sign, a reflex response that signals dysfunction in the corticospinal pathways. Brain and spinal magnetic resonance imaging showed no structural abnormalities, pointing the diagnostic workup away from stroke, tumor, or spinal cord compression and toward a molecular culprit.

Laboratory testing supplied it. Her serum carried markedly elevated levels of anti-glutamic acid decarboxylase antibodies, measured at 132,000 U/mL, and her cerebrospinal fluid contained the same antibodies at 3,520 U/mL without pleocytosis, an elevation of white cells that would suggest infection or inflammation of another kind. Glutamic acid decarboxylase is the enzyme that manufactures gamma-aminobutyric acid, the principal inhibitory neurotransmitter of the central nervous system. When antibodies attack the enzyme, GABAergic neurotransmission falters, and the nervous system loses much of its ability to dampen muscle contraction, producing the rigidity and spasms that define the syndrome. Anti-GAD antibodies are detected in approximately 70 to 80% of patients with stiff-person syndrome, and the condition frequently coexists with other autoimmune diseases, including type 1 diabetes mellitus and Hashimoto’s thyroiditis.

Two further findings sharpened the picture. Serum anti-acetylcholine receptor antibodies were weakly positive, yet the patient showed no clinical manifestations suggestive of myasthenia gravis, another autoimmune condition strongly linked to thymoma. Anti-amphiphysin antibodies, which mark the classical paraneoplastic form of the syndrome seen with breast cancer or small-cell lung carcinoma, were negative. The authors argue that this combination, weak anti-AChR positivity without myasthenia alongside absent anti-amphiphysin antibodies, supported a thymoma-related autoimmune background, reflecting immune dysregulation driven by thymic epithelial tumors rather than the antibody profile typical of cancer-associated disease.

Imaging then located the suspected trigger. Contrast-enhanced chest computed tomography identified a 13 by 10 by 2 millimeter anterior mediastinal nodule with heterogeneous enhancement, and chest magnetic resonance imaging showed focal high-intensity areas on T2-weighted sequences with mild peripheral enhancement after gadolinium. Based on these findings, clinicians suspected paraneoplastic stiff-person syndrome associated with thymoma. Before surgery, the team stabilized her neurologically. High-dose intravenous methylprednisolone, intravenous immunoglobulin, baclofen, and diazepam brought rapid improvement in lower limb pain, and spasticity gradually lessened, though it persisted. She still required assistance to stand and could not walk independently, so after a multidisciplinary discussion the prednisolone dose was tapered to 10 mg per day and bilateral thoracoscopic extended thymectomy was scheduled.

The operation itself was uncomplicated. Surgeons began on the right side to clearly identify the left brachiocephalic vein, found the tumor free of invasion into surrounding tissues, and achieved complete resection. The procedure took 3 hours and 1 minute with an estimated blood loss of 34 milliliters. Histopathological examination revealed a nodular lesion predominantly composed of lymphocytes within mature adipose tissue, and immunohistochemical staining showed a reticular network of keratin-positive epithelial cells and immature TdT-positive lymphocytes, the signature of thymoma. The final diagnosis was WHO type B1 thymoma at Masaoka stage I with complete R0 resection. Macroscopically the resected tumor was grayish-white and measured approximately 20 millimeters in diameter.

Recovery was neither linear nor instant, and the report is candid about that. The patient continued intensive rehabilitation, was discharged on postoperative day 32 ambulating with a cane, and then experienced temporary worsening, with increased spasticity and a higher stiffness index that required readmission. Her symptoms improved after treatment with methylprednisolone. Laboratory tests before discharge showed anti-GAD antibody levels of 124,000 U/mL in serum and 3,470 U/mL in cerebrospinal fluid, a downward trend from preoperative values but still markedly elevated. Serum levels remained above 5,000 U/mL throughout follow-up. Yet function improved steadily, and by two years after surgery she walked independently, climbed stairs without assistance, and no longer needed diazepam, remaining on prednisolone at 10 mg per day with stable neurological symptoms while gradual tapering was considered.

The authors place this outcome in a wider context by reviewing the literature. To date, 16 surgically treated cases of thymoma-associated stiff-person syndrome have been reported. Most patients were anti-GAD antibody-positive, 15 of 16, and anti-AChR antibodies were present in 7 of 16. Coexisting autoimmune diseases were frequent, with myasthenia gravis the most common, present at diagnosis in three cases and developing postoperatively in two. Pure red cell aplasia and autoimmune thyroiditis were also reported. Surgical outcomes were generally favorable, with many patients showing neurological improvement, but postoperative relapse or exacerbation occurred in nine patients, 56%, including the present case. The authors conclude that surgery alone may not immediately stabilize the syndrome and that adjunctive immunotherapy is often required. Because the number of thoracoscopic and robotic cases remains small, they caution that firm conclusions about the influence of surgical approach on neurological outcomes are not yet possible, and available evidence suggests postoperative exacerbation relates more strongly to disease severity, bulbar involvement, and the adequacy of perioperative immunomodulatory management than to the approach itself.

Why operate at all if antibody titers stay high? The authors note that extended thymectomy was the predominant surgical strategy in reported cases, with WHO type B1 and B2 the most common histological subtypes, mirroring thymomas associated with myasthenia gravis. Because relapse of the syndrome has been reported after thymoma recurrence, achieving R0 resection matters for both neurological and oncological control, and removing the thymus may reduce residual thymic tissue that could harbor autoreactive T cells, potentially mitigating ongoing immune dysregulation. Previous studies have shown poor correlation between antibody titers and clinical severity, which supports functional status as the more relevant indicator of treatment response. In this case, extended thymectomy produced sustained functional improvement despite persistently elevated anti-GAD antibody titers, and the patient achieved independent ambulation and improved quality of life. The weak anti-AChR positivity nonetheless signals the need for long-term surveillance for myasthenia gravis, syndrome relapse, or thymoma recurrence. The authors acknowledge the limits of a single-case design and the small number of comparable cases in the literature, noting that further accumulation is needed to clarify optimal surgical timing, perioperative immunotherapy, and long-term neurological outcomes. Their conclusion is measured: extended thymectomy may contribute to sustained neurological and functional improvement in selected patients with thymoma-associated stiff-person syndrome, even when anti-GAD antibody titers remain elevated, and surgical treatment should be integrated into a multidisciplinary strategy that balances oncological radicality with individualized neurological stabilization.

Subject of Research: A case report of thymoma-associated stiff-person syndrome treated with extended thymectomy

Article Title: Thymoma-associated stiff-person syndrome successfully treated with extended thymectomy: a case report

Article References: Maita, K., Higeta, T., Watanabe, H., Nakano, T., Tokuoka, K., Nakagawa, T., Nogawa, S., Yamada, S., & Masuda, R. (2026). Thymoma-associated stiff-person syndrome successfully treated with extended thymectomy: a case report. General Thoracic and Cardiovascular Surgery Cases, 5(1), Article 32. https://doi.org/10.1186/s44215-026-00264-3

Image Credits: AI Generated

DOI: 10.1186/s44215-026-00264-3

Keywords: stiff-person syndrome, thymoma, extended thymectomy, anti-GAD antibodies, paraneoplastic neurological disorder, autoimmune disease, thoracic surgery, GABAergic neurotransmission, case report, immunotherapy, myasthenia gravis surveillance, Thymoma-associated