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: Progressive dementia, vertical ophthalmoplegia, and prominent hypothalamic dysfunction developed in one patient with documented intestinal Whipple's disease despite ongoing antibiotic therapy with intestinal remission. A clinical diagnosis of central nervous Whipple's disease was made on the basis of the patient's presentation. High-dose parenteral penicillin and chloramphenicol were administered for 41/2 weeks. There was no improvement in results of daily mental status examination or neuropsychologic testing. Deterioration was noted in the electroencephalographic findings after therapy. Vigorous antibiotic therapy with agents that cross the blood-brain barrier had no immediate beneficial effect. Irreversible neurologic damage or a slow, delayed response may account for this observation.

(C) 1981 American College of Physicians