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Stiff-person syndrome associated with invasive thymoma: a case report

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Abstract

We report a case of a 40-year-old female with continuous muscle stiffness and painful muscle spasms. The symptoms worsened over a two-week period after onset. Electrophysiological examinations revealed continuous muscle discharge, which was markedly reduced by intravenous administration of diazepam. High levels of anti-glutamic acid decarboxylase (GAD) antibodies were detected in both serum and cerebrospinal fluid, suggesting that the patient suffered from stiff-person syndrome. Steroid pulse therapy and immunoadsorption therapy alleviated the clinical symptoms and decreased the anti-GAD antibody titer. A chest CT revealed the presence of an invasive thymoma. Neither anti-acetylcholine receptor (AChR) antibodies nor symptoms of myasthenia gravis (MG) were observed. The patient underwent a thymectomy and postoperative radiotherapy. These treatments further alleviated the clinical symptoms. The present case is the first that associates stiff-person syndrome with invasive thymoma, and not accompanied by MG. The autoimmune mechanism, in this case, may be triggered by the invasive thymoma.

Introduction

Stiff-person syndrome is a rare, distressing neurological disorder that is characterized by continuous systemic muscle stiffness and painful paroxysmal muscle spasms [1], [2], [3]. The symptoms usually begin with tightness or stiffness of the trunk muscles, which may slowly spread to the proximal muscles of the extremities. In addition to muscle stiffness, painful paroxysmal muscle spasms are precipitated by sudden movement, sound, tactile stimulation, or emotional upset. The pathogenesis of the stiff-person syndrome is not fully understood. Neuropharmacological studies have shown evidence of an imbalance between catecholamine excitatory and γ-aminobutyric acid (GABA) inhibitory neurotransmitter systems in the brainstem and spinal cord. In support of this hypothesis, 50–60% of patients with stiff-person syndrome were reported to have autoantibodies to glutamic acid decarboxylase (GAD), which catalyses the conversion of glutamate to GABA, present in both serum and cerebrospinal fluid [4], [5]. Stiff-person syndrome has been associated with autoimmune diseases such as insulin-dependent diabetes mellitus (IDDM), Graves' disease, Hashimoto's thyroiditis, pernicious anemia [5], [6], [7]. In addition, stiff-person syndrome is reported to be associated with adenocarcinoma of the breast, adenocarcinoma of the colon, Hodgkin's lymphoma, small-cell carcinoma of the lung, pharyngeal carcinoma, mediastinal tumor and thymoma [8], [9], [10], [11], [12], [13], [14]. Here, we describe a case of stiff-person syndrome associated with invasive thymoma that is not accompanied by myasthenia gravis (MG).

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Case report

A 40-year-old female clerical worker was admitted to our hospital complaining of stiffness in the bilateral lower extremities and a gait disturbance. She has no history of diabetes, injuries or epilepsy. In addition, there is no history of intermarriage in her family. Her mother has a history of dialysis, but details are unknown. The patient's life history is unremarkable. On May 22, 1999, the patient experienced vertigo, pharyngeal pain, dysphagia, and dysarthria. On May 30, she began to fall

Discussion

In this case, the patient was presented with continuous muscle stiffness and painful muscle spasms that either occurred spontaneously or were precipitated by sensory stimuli. Continuous muscle discharge was detected in the electrophysiological examinations, but these discharges were markedly decreased by the administration of intravenous diazepam. The anti-GAD antibody level was high in both serum and cerebrospinal fluid. The anti-pancreatic islet cell antibodies were negative. Since islet

Acknowledgements

We thank Dr. Meiko Shiina, from our department, for performing Western blot analysis.

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1

Present address: Department of Neuroscience, Brown University, Box 1953, 190 Thayer Street, Providence, Rhode Island, 02912, USA.

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