Multifocal Myoclonus Induced by Trimethoprim–Sulfamethoxazole Therapy in a Patient with Nocardia Infection
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《新英格兰医药杂志》
To the Editor: A 63-year-old woman with a history of non-Hodgkin's lymphoma that had been treated 25 years previously, as well as a history of hypertension, hypercholesterolemia, transient ischemic attack, and acute myelogenous leukemia with induction of remission three months previously, was admitted to our hospital with a five-day history of fever, fatigue, decreased appetite, and leukocytosis (white-cell count, 18,000 per cubic millimeter), without evidence of a recurrence of leukemia. Blood cultures grew Nocardia asteroides. The patient had no skin lesions or new focal neurologic signs. A computed tomographic scan of the chest revealed multiple new bilateral nodules. The patient refused bronchoscopy. Sputum cultures were negative for fungus. Magnetic resonance images (MRI) of the brain showed extensive, bilateral small-vessel disease without acute infarction. She was started on a regimen of 20 mg of trimethoprim per kilogram of body weight per day and 100 mg of sulfamethoxazole per kilogram per day, given intravenously in two doses, and 2 g of ceftriaxone given twice daily.
The fever abated, and four days later, the patient began to have progressively worsening involuntary movements involving the head and all extremities. Neurologic examination revealed diffuse, multifocal myoclonus and bilateral asterixis, with no other abnormalities. The serum levels of glucose, electrolytes, thyroid hormones, vitamin B12, and folate were normal. The patient refused lumbar puncture. Repeated MRI examination of the brain revealed no new changes. The trimethoprim–sulfamethoxazole was stopped, and the involuntary movements decreased markedly the following day; by the fourth day, they had resolved completely. The patient remained afebrile, and her condition continued to improve with the use of intravenous ceftriaxone.
The occurrence of multifocal myoclonus and asterixis induced by treatment with trimethoprim–sulfamethoxazole is very rare. Previous reports have described reversible tremors in patients with AIDS who were being treated with trimethoprim–sulfamethoxazole for Pneumocystis carinii pneumonia.1,2,3 Only one report has described tremors induced by trimethoprim–sulfamethoxazole in an immunocompetent patient.4 In these patients, tremors occurred within 3 to 8 days after the initiation of treatment and resolved within 10 days after its discontinuation. This rare complication is dose-related and is not immunologic. The specific mechanism by which trimethoprim–sulfamethoxazole induces tremors is not fully understood; dihydrofolate reductase inhibition may affect dopamine metabolism in the central nervous system.5
Our patient was immunocompromised as a result of recent chemotherapy and was receiving a high dose of trimethoprim–sulfamethoxazole. Our findings emphasize that clinicians should be aware of the possible occurrence of myoclonus and asterixis, as well as tremors, in patients who are receiving a high dose of this drug combination. This rare effect might be underdiagnosed, and a trial of discontinuation of trimethoprim–sulfamethoxazole should be considered before a costly neurologic evaluation is performed.
Elie G. Dib, M.D.
Steven Bernstein, M.D.
Curtis Benesch, M.D.
University of Rochester School of Medicine and Dentistry
Rochester, NY 14642
elie_dib@urmc.rochester.edu
References
Borucki MJ, Matzke DS, Pollard RB. Tremor induced by trimethoprim-sulfamethoxazole in patients with acquired immunodeficiency syndrome (AIDS). Ann Intern Med 1988;109:77-78.
Van Gerpen JA. Tremor caused by trimethoprim-sulfamethoxazole in a patient with AIDS. Neurology 1997;48:537-538.
Aboulafia DM. Tremors associated with trimethoprim-sulfamethoxazole therapy in a patient with AIDS: case report and review. Clin Infect Dis 1996;22:598-600.
Patterson RG, Couchenour RL. Trimethoprim-sulfamethoxazole-induced tremor in an immunocompetent patient. Pharmacotherapy 1999;19:1456-1458.
Woody RC, Brewster MA. Adverse effects of trimethoprim-sulfamethoxazole in a child with dihydropteridine reductase deficiency. Dev Med Child Neurol 1990;32:639-642.
The fever abated, and four days later, the patient began to have progressively worsening involuntary movements involving the head and all extremities. Neurologic examination revealed diffuse, multifocal myoclonus and bilateral asterixis, with no other abnormalities. The serum levels of glucose, electrolytes, thyroid hormones, vitamin B12, and folate were normal. The patient refused lumbar puncture. Repeated MRI examination of the brain revealed no new changes. The trimethoprim–sulfamethoxazole was stopped, and the involuntary movements decreased markedly the following day; by the fourth day, they had resolved completely. The patient remained afebrile, and her condition continued to improve with the use of intravenous ceftriaxone.
The occurrence of multifocal myoclonus and asterixis induced by treatment with trimethoprim–sulfamethoxazole is very rare. Previous reports have described reversible tremors in patients with AIDS who were being treated with trimethoprim–sulfamethoxazole for Pneumocystis carinii pneumonia.1,2,3 Only one report has described tremors induced by trimethoprim–sulfamethoxazole in an immunocompetent patient.4 In these patients, tremors occurred within 3 to 8 days after the initiation of treatment and resolved within 10 days after its discontinuation. This rare complication is dose-related and is not immunologic. The specific mechanism by which trimethoprim–sulfamethoxazole induces tremors is not fully understood; dihydrofolate reductase inhibition may affect dopamine metabolism in the central nervous system.5
Our patient was immunocompromised as a result of recent chemotherapy and was receiving a high dose of trimethoprim–sulfamethoxazole. Our findings emphasize that clinicians should be aware of the possible occurrence of myoclonus and asterixis, as well as tremors, in patients who are receiving a high dose of this drug combination. This rare effect might be underdiagnosed, and a trial of discontinuation of trimethoprim–sulfamethoxazole should be considered before a costly neurologic evaluation is performed.
Elie G. Dib, M.D.
Steven Bernstein, M.D.
Curtis Benesch, M.D.
University of Rochester School of Medicine and Dentistry
Rochester, NY 14642
elie_dib@urmc.rochester.edu
References
Borucki MJ, Matzke DS, Pollard RB. Tremor induced by trimethoprim-sulfamethoxazole in patients with acquired immunodeficiency syndrome (AIDS). Ann Intern Med 1988;109:77-78.
Van Gerpen JA. Tremor caused by trimethoprim-sulfamethoxazole in a patient with AIDS. Neurology 1997;48:537-538.
Aboulafia DM. Tremors associated with trimethoprim-sulfamethoxazole therapy in a patient with AIDS: case report and review. Clin Infect Dis 1996;22:598-600.
Patterson RG, Couchenour RL. Trimethoprim-sulfamethoxazole-induced tremor in an immunocompetent patient. Pharmacotherapy 1999;19:1456-1458.
Woody RC, Brewster MA. Adverse effects of trimethoprim-sulfamethoxazole in a child with dihydropteridine reductase deficiency. Dev Med Child Neurol 1990;32:639-642.