Short communicationStiff-person syndrome associated with invasive thymoma: a case report
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).
Section snippets
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.
References (20)
- et al.
A critical survey of stiff-man syndrome
Am. J. Med.
(1967) - et al.
Stiff-man syndrome updated
Mayo Clin. Proc.
(1989) Neurologic paraneoplastic syndromes
J. Neurol. Sci.
(1998)- et al.
Thymoma: a study of the pathologic classification of 71 cases with evaluation of the Muller-Hermelink system
Human Pathol.
(1993) - et al.
The clinicopathological correlation of epithelial subtyping in thymoma: a study of 112 consecutive cases
Hum. Pathol.
(1994) - et al.
Progressive fluctuating muscular rigidity and spasm (“stiff-man” syndrome)—report of a case and some observation in 13 other cases
Mayo Clin. Proc.
(1956) - et al.
Autoantibodies to glutamic acid decarboxylase in a patient with stiff-man syndrome, epilepsy, and type I diabetes mellitus
N. Engl. J. Med.
(1988) - et al.
Autoantibodies to GABA-ergic neurons and pancreatic beta cells in stiff-man syndrome
N. Engl. J. Med.
(1990) Movement disorders of autoimmune origin
J. Neurol.
(1999)- et al.
The stiff-person syndrome: an autoimmune disorder affecting neurotransmission of gamma-aminobutyric acid
Ann. Intern. Med.
(1999)
Cited by (43)
A systematic review of paraneoplastic syndromes associated with thymoma: Treatment modalities, recurrence, and outcomes in resected cases
2020, Journal of Thoracic and Cardiovascular SurgeryThe neurological syndromes associated with glutamic acid decarboxylase antibodies
2019, Journal of AutoimmunityCitation Excerpt :However, the pathogenic role of such coexisting Abs is unclear. Encephalitis (n = 6) and CA (n = 4) were the most common syndromes presenting as PNS, contrasting with previous published reports, indicating that SPS is the most common anti-GAD syndrome associated with cancer [101–103]. In another study, which included 41 patients with anti-GAD CA, diverse types of cancer were identified in 22% of these patients [104].
Treatment and Management of Disorders of Neuromuscular Hyperexcitability
2011, Neuromuscular DisordersTreatment and Management of Disorders of Neuromuscular Hyperexcitability
2010, Neuromuscular Disorders: Treatment and ManagementThymoma, Myasthenia Gravis, and Other Paraneoplastic Syndromes
2008, Hematology/Oncology Clinics of North AmericaCitation Excerpt :The most common serologic markers of stiff person syndrome are antiglutamic acid decarboxylase (GAD) antibodies and anti-amphiphysin antibodies. Stiff person syndrome has been reported in association with thymoma and anti-GAD antibodies [68]. Stiff person syndrome associated with anti-amphiphysin antibodies is more likely paraneoplastic in etiology and should prompt a radiologic evaluation for neoplasm.
Neuromuscular Complications of Cancer and Cancer Treatments
2008, Physical Medicine and Rehabilitation Clinics of North AmericaCitation Excerpt :Treatment can also involve the use of cholinesterase inhibitors or immunosuppressive agents. Hyperactivity syndromes, such as Stiff-person syndrome or neuromyotonia (Isaac's syndrome), are rare but have been associated with malignancies, including small-cell lung cancer, breast cancer, lymphoma, and invasive thymoma [26–28]. Stiff-person syndrome is a disorder characterized by muscle rigidity and a worsening of symptoms with exposure to certain triggers, such as loud noise or startle.
- 1
Present address: Department of Neuroscience, Brown University, Box 1953, 190 Thayer Street, Providence, Rhode Island, 02912, USA.