Correspondence

Reversible Dementia Due to Thalidomide Therapy for Multiple Myeloma

N Engl J Med 2003; 348:1821-1822May 1, 2003

Article

To the Editor:

Thalidomide is used to treat multiple myeloma because of its apoptotic1 and antiangiogenic2 properties. Common side effects of thalidomide in patients with multiple myeloma include sedation and peripheral neuropathy.3 We describe a case of reversible dementia due to thalidomide therapy for multiple myeloma.

A 66-year-old man with a history of coronary artery disease received a diagnosis of multiple myeloma in August 2001. In April 2002, he began a chemotherapy regimen of thalidomide (200 mg orally once a day) and dexamethasone (40 mg orally once a day on days 1 through 4, 9 through 12, and 17 through 20 each month). In June 2002, he became forgetful and manic. The patient, a lawyer with no previous psychiatric history, was evaluated, and dexamethasone treatment was discontinued. Risperidone (2 mg orally twice a day) was prescribed, and the mania resolved shortly thereafter. In July 2002, the patient had an increase in memory loss. At this time, risperidone treatment was discontinued at another hospital. The patient's wife observed no improvement as a result of this change in the regimen.

In August 2002, the patient was admitted to the Medical College of Virginia Hospital for evaluation of his mental status. At this time, his wife reported that he had forgotten how to brush his teeth and how to take a shower. On evaluation, the patient was afebrile, with no focal neurologic deficits. He was alert but not oriented to person, place, or time. He could not recall the names of family members (his wife and children) or recent historical events. However, he did recall three of three words at one and five minutes. His score on the Mini–Mental State Examination was 23 out of 30 (the median score for persons of his age and level of education is 29 out of 30). The results of a complete blood count, a urine drug test, and a rapid test of plasma reagin; measurements of serum electrolytes (including calcium), thyrotropin, vitamin B₁₂ and folate, and serum ammonia; and the findings on electroencephalography and computed tomography and magnetic resonance imaging of the brain were all within normal limits.

Two days after admission, a subtle resting tremor was noted — a reported side effect of thalidomide.3 Thalidomide therapy was discontinued and the patient had complete resolution of dementia within 48 hours.

The patient had memory loss shortly after the commencement of chemotherapy for multiple myeloma, which later progressed to disorientation, apraxia, and tremor. An extensive evaluation revealed no medical cause. Discontinuation of thalidomide therapy because of tremor, a known side effect, was followed by rapid recovery of memory and other cognitive functions. Physicians should consider the possibility that thalidomide may induce reversible dementia in patients with multiple myeloma.

Alexander E. Morgan, M.D.
Wade K. Smith, M.D.
James L. Levenson, M.D.
Virginia Commonwealth University Medical Center, Richmond, VA 23298
aem22@drexel.edu

3 References

1. 1

   Mitsiades N, Mitsiades CS, Poulaki V, et al. Apoptotic signaling induced by immunomodulatory thalidomide analogs in human multiple myeloma cells: therapeutic implications. Blood 2002;99:4525-4530
   CrossRef | Web of Science | Medline

2. 2

   Moehler TM, Neben K, Ho AD, Goldschmidt H. Angiogenesis in hematologic malignancies. Ann Hematol 2001;80:695-705
   CrossRef | Web of Science | Medline

3. 3

   Weber D, Rankin K, Gavino M, Delasalle K, Alexanian R. Thalidomide alone or with dexamethasone for previously untreated multiple myeloma. J Clin Oncol 2003;21:16-19
   CrossRef | Web of Science | Medline

Citing Articles (6)

Citing Articles

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   Y. Cao, J. Arbiser, R. J. D'Amato, P. A. D'Amore, D. E. Ingber, R. Kerbel, M. Klagsbrun, S. Lim, M. A. Moses, B. Zetter, H. Dvorak, R. Langer. (2011) Forty-Year Journey of Angiogenesis Translational Research. Science Translational Medicine 3:114, 114rv3-114rv3
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   2006. Thalidomide. , 3343-3360.
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3. 3

   John C Morgan, Kapil D Sethi. (2005) Drug-induced tremors. The Lancet Neurology 4:12, 866-876
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4. 4

   Morie A. Gertz, Martha Q. Lacy, Angela Dispenzieri, Suzanne Hayman. (2005) Current status of stem cell transplantation for multiple myeloma. Current Treatment Options in Oncology 6:3, 229-240
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   Emmanuel Laffitte, Jean Revuz. (2004) Thalidomide: an old drug with new clinical applications. Expert Opinion on Drug Safety 3:1, 47-56
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   (2003) Current awareness: Pharmacoepidemiology and drug safety. Pharmacoepidemiology and Drug Safety 12:7, 617-632
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