Therapeutic Drugs

As the development of new drugs for treating medical diseases steadily advances, so does the potential for toxicity from these agents. Many new drugs have been found to cause leukoencephalopathy, although the mechanism by which this toxicity occurs is obscure.

a. Chemotherapeutic Agents As in the case of cerebral irradiation, the white matter is the target of many of the pharmaceutical agents used in the treatment of cancer. The growing list of antineoplastic agents associated with leukoencephalopathy results in part from improved supportive care of cancer patients that has permitted higher doses and longer survival periods during which adverse effects may appear.

In general, these drugs cause a syndrome that is clinically, neuroradiologically, and neuropathologi-cally similar to radiation leukoencephalopathy. Neu-robehavioral features are particularly characteristic and may include lassitude, drowsiness, confusion, memory loss, and dementia. Methotrexate was the first antineoplastic drug found to cause leukoencephalo-pathy, which is its most common and significant toxicity. 1,3-Bis(2-chloroethyl)-1-nitrosourea is also well recognized to cause white matter changes. Other drugs have often been recognized as white matter toxins because of findings on MRI. Little is known of treatment other than minimization of exposure and supportive care.

b. Immunosuppressive Agents Organ transplana-tion has become commonplace in recent decades, and immunosuppression has become a necessary component of postoperative care to prevent organ rejection. Two drugs, cyclosporine and tacrolimus, have been associated with leukoencephalopathy. Reversibility has been observed with cessation of therapy.

c. Antimicrobials Two antimicrobial agents may result in leukoencephalopathy. Amphotericin B is a mainstay of fungal infection treatment, and white matter damage is one of its many toxicities. Hexa-chlorophene is an antiseptic agent that can cause this syndrome if absorbed through the skin in sufficient quantity.

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