Stiff-person syndrome after thymectomy in myasthenia gravis mimicking a post-thymectomy myasthenic crisis
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/neuroindia.NI_493_16
Source of Support: None, Conflict of Interest: None
Stiff-person syndrome (SPS) is a rare neurological disorder, which is characterized by continuous systemic muscle stiffness and painful paroxysmal spasm with co-contraction of agonist and antagonist muscles. Most patients with SPS have antibodies directed against the enzyme glutamic acid decarboxylase (GAD), which can be used to confirm the diagnosis of SPS.,
We present a case of SPS after thymectomy in a patient with myasthenia gravis (MG). To our knowledge, this is the first report of SPS after thymectomy associated with MG.
A 48-year old woman attended the emergency room because of generalized weakness with dyspnea. Two months previously, she had been diagnosed with MG. The thymoma was revealed on computer tomography, and thymectomy was performed 1 month prior to the current admission. The histology of the thymoma was of cortical type, World Health Organization (WHO) grade B1 (Masaoka grade I). Her neurological examination during the visit showed bilateral ptosis, dyspnea, and generalized weakness with intermittent muscle stiffness. Arterial blood gas analysis showed respiratory acidosis. A diagnosis of MG crisis after thymectomy was made and intravenous immunoglobulin G (IVIG) therapy was started together with ventilator care. However, the patient complained of frequent painful muscle spasms. One month after IVIG therapy, all her symptoms improved.
Four months after IVIG therapy, she was readmitted with dyspnea with muscle stiffness and painful spasms. She showed co-contraction of agonist and antagonist muscles in the abdomen and thorax. The motor examination showed proximal weakness caused by MG. Anti-acetylcholine receptor antibody (Anti-AchR) antibody was elevated to 10.184 nmol/L and anti-GAD (glutamic acid decarboxylase) antibody was 300 U/mL (reference range: <1.0 U/mL). Magnetic resonance imaging of the head and spinal cord revealed no abnormality and electroencephalography and nerve conduction studies were normal. Finally, she was diagnosed with SPS. She was treated with IVIG therapy, which relieved the clinical symptoms.
SPS is a rare neurologic syndrome that is frequently found in association with autoimmune disorders or tumors. However, post-thymectomy MG crises are not uncommon; the incidence varies from 3.1 to 30.3%. This patient was initially diagnosed with a post-thymectomy MG crisis because her dyspnea requiring mechanical ventilation developed within one month after thymectomy. However, she also complained of muscle stiffness and cramps, and was therefore, finally diagnosed with SPS after thymectomy in MG.
Only 4 cases of coexisting SPS and MG with thymoma have been reported previously [Table 1].,,, In these cases, SPS developed before the symptoms of MG and the thymoma was discovered in the process of evaluating the cause of the SPS; moreover, the symptoms of SPS improved in all these patients after thymectomy. It is interesting that our patient was diagnosed with MG with thymoma, and subsequently, SPS developed after thymectomy. Unlike the previous cases, the serology showed that our patient was positive for both anti-GAD and anti-AchR antibodies.
The pathogenesis of SPS is not fully understood. Neuropharmacological studies have shown evidence of an imbalance between catecholamine excitatory and gamma-aminobutyric acid inhibitory neurotransmitter systems in the brainstem and spinal cord.
There have been several reports of post-thymectomy MG where patients developed myasthenic symptoms after thymectomy. It was suggested that large numbers of mature autoantigen-specific T cells enter the peripheral blood and that these cells can persist in the periphery for many years, even though thymectomy has been performed. Therefore, considering that, in our patient, SPS developed after thymectomy, it is possible that other paraneoplastic antibodies such as the anti-GAD antibody associated with thymoma may persist for several years after thymectomy.
In addition, there have been recent reports that a systemic autoimmune disease developed after thymectomy in patients with MG or other immunological diseases, suggesting that there was a marked acceleration of the disease possibly caused by the elimination of the thymic T-suppressor cell population. Therefore, the development of SPS after thymectomy could be associated with an autoimmune mechanism.
There is no established standard therapy for SPS. Various agents including benzodiazepines, antispasmodic agents, intramuscular botulinum toxin A, antiepileptic drugs, and immunosuppressive agents have been used. We treated our patient with IVIG and steroid pulse therapy for the aggravation of SPS, and with multiple drugs for symptomatic management.
This is the first report of a patient with MG and thymoma, who developed SPS after thymectomy and had both anti-GAD and anti-AchR antibodies. These paraneoplastic syndromes may both be the result of an autoimmune mechanism that is associated with thymoma. Initially, the patient's symptoms mimicked those of a postoperative MG crisis; however, her muscle stiffness was eventually determined to be caused by SPS.
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