J. Exp. Clin. Cancer Res., 23, 2, 2004
Case Report
Myasthenic Crisis Following Cisplatin Chemotherapy in a Patient with Malignant Thymoma Y. Solak1, O. Dikbas2, K. Altundag2, N. Guler2, Y. Ozisik2 Dept. of Internal Medicine1, Dept. of Medical Oncology2, Hacettepe University Faculy of Medicine, Ankara, Turkey
Malignant thymomas are associated with numerous autoimmune disorders including myasthenia gravis. Myastenia gravis is characterized by antibodies against the acetylcholine receptors located on the neuromuscular junction of the skeletal muscle. We present a case with malignant thymoma who developed myasthenia crisis while he was treated with cisplatin chemotherapy. Key Words: Malignant thymoma, Myasthenia gravis, Cisplatin
Thymomas make up 20% of mediastinal tumors. Thirty percent of thymomas are invasive and have metastatic capacity. Thymomas with invasive and metastatic bahaviour are generally treated with combination chemotherapy in addition to surgery and radiotherapy. Myastenia gravis is an autoimmune disorder, characterised by antibodies opposed to the skeletal muscle (1). It is clinically characterised by weakness of the skeletal muscles, especially extraocular muscles. Typical symptoms are slurred speech, dysphagia, dysphonia, dysartria, ptosis, and respiratory insufficiency; even respiratory failure in case of advanced disease (2). The patient feels better in the morning, but symptoms progress during day time. Intervening infections, accidents, operations deteriorate the symptoms of the disease (3). These factors may lead to the myastenic crisis (3). Treatments used for the myasthenia gravis are immunosupressive drugs, acetylcholine esterase inhibitor drugs, thymectomy, plasma exchange, intravenous immunoglobulin (4). Myasthenic crisis is a life threatening condition which occurs in patients with myastenia gravis when symptoms progress to a point where respiratory support is required (5). Myasthenia gravis occurs in patients with thymic tumors, lymphoma, small cell lung cancer, chordoma, pheochromocytoma. Non neoplastic conditions such as: pernicious anemia, romatoid artritis, systhemic lupus erithematosis, polymyositis may also accompany myasthenia gravis.
Case Report A forty-five year old male was admitted to the hospital to undergo chemotherapy consisting of a single agent cisplatin. His past history stated that he had a diagnosis of locally, invasive thymoma with the symptoms of myasthenia gravis 2 years before and was treated with combination chemotherapy consisting of cisplatin 50 mg/m2, adriamycin 50 mg/m2 and cyclophosphamide 500mg/m2, day 1 every 21 days. He received 6 cycles of chemotherapy and then external radiotherapy was applied. Radiological evaluation showed partial response and he was followed without any treatment with 3 monthly controls until he developed myasthenic symptoms. Myasthenic symptoms were controlled with pyridostigmin, azathioprin and steroid. A thorax computerized tomography showed progression of the primary lesion. Single agent cisplatin 35mg/m2 days 1 and 2 every 21 days was initiated. He was discharged while he was taking the medications consisting of pyridostigmin, azathioprin and steroid for myasthenic symptoms. One week following chemotherapy the patient was admitted to our emergency department complaining of persistent nausea and vomiting. In the course of the follow-up, his respiration shallowed and arterial oxygen saturation reduced to 50%. Elective intubation was performed and steroid dose was increased. The level of the antiacetylcholine antibody in serum was 74 nmol/liter 343
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(Normal is < 0.5 nmol/liter). The plasmapheresis was performed to accelerate the weaning process from the mechanical ventilation. He was extubated after 2 weeks of intubation. Plasmapheresis was performed on alternate days, totally for five times. He was then discharged without any symptoms related to myastenia gravis. Discussion Myastenia gravis is diagnosed by clinical findings and detection of an increased anti-acetylcholine receptor antibody level. This antibody, however, is not obligatory for the diagnosis of myasthenia gravis. Myasthenia gravis commonly occurs with other autoimmune disorders such as systemic lupus erythematosis, rheumatoid arthritis, pernicious anemia, polymyositis, pemphigus (6). Myasthenic crisis is a life threatening complication of Myasthenia Gravis. The most probable triggering factors are change in medication, factors that prevent taking medications, intervening infections (especially respiratory tract infections), physical and emotional stress, cardiac disease and surgery (3). Differential diagnosis of the myasthenic crisis includes electrolyte abnormalities, Guillain-Barre Syndrome, motor neuron disease, organophosphate toxicity, botulism, acetylcholine esterase inhibitor overdose, Eaton Lambert Syndrome and a mass compressing the cervical cord or the brain stem (3). Thymic tumors either benign or malignant, lymphoma, small cell lung carcinoma, breast cancer, thyroid cancer are frequently associated with myasthenia gravis. Thymectomy is the primer therapeutic modality for myastenia gravis. Inoperability, insufficient control of symptoms following thymectomy and disease caused by non-thymic neoplasms are treated with immunosupressive therapy, plasmapheresis or intravenous immunoglobulins. Steroids are a good choice for first line immunosupressive therapy. If it is compared with steroids, azothiopyrine is a good choice with less side effects and better tolerability. When thymectomy and immunosupressive therapy fails or is not tolerated by the patient, plasmapheresis or intravenous immunoglobulin appears to be an excellent alternative. Intravenous immunoglobulin instead of
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plasmapheresis, seems to be a better choice in elders or in patients with poor peripheral venous access (5). Intravenous anticholine esterase antibody treatment is another alternative for myastenic chrisis (6). Plasma exchange is preferred in the management of patients who are under mechanical ventilation. It has some advantage of improving muscle strength, increasing the speed of weaning from the mechanical ventilation, reducing the anticholinesterase dose required for the patient. Our patient succesfully improved following plasma exchange. In our case, intractable vomiting due to cisplatin failed the regular intake of the pills for myasthenia gravis and posed the patient into myasthenic crisis. One should be aware of the fact that myasthenic crisis may occur due to chemotherapy induced uncontrolled emesis that causes inability to take oral pills in patients with invasive thymoma with the symptoms of myasthenia gravis. References 1. Drachman D.B.: Myasthenia gravis. N. Engl. J. Med. 330:1797-1810, 1994. 2. Sharp H.R., Degrip A., Mitchell D.B., Heller A.: Bulbar presentation of myasthenia gravis in the elderly patient. J. Laryngol. Otol. 115:1-3, 2001. 3. Bedlack R.S., Sanders D.B.: How to handle myasthenic crisis: Essential steps in patient care. Postgrad. Med. 107:211-214, 220-222, 2000. 4. Rivner M.H.: Steroid treatment for myasthenia gravis: steroids are overutilized. Muscle Nerve 25:115-117, 2002. 5. Thomas C.E., Mayer S.A., Gungor Y., Swarup R., Webster E.A., Chang I., Brannagan T.H., Fink M.E., Rowland L.P.: Myasthenic crisis: clinical features, mortality, complications, and risk factors for prolonged intubation. Neurology 48:12531260, 1997. 6. Borel C.O.: Management of myasthenic crisis: Continious anticholinesterase infusion. Crit. Care Med. 21:821-822, 1993.
Received: June 4, 2003 Kadri Altundag, MD 8181 Fannin Street No: 728 Houston, Texas 77054 U.S.A. Tel.: +1-713-7950438; Fax: +1-713-7944385 E-mail:
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