Whipple disease of the central nervous system.

In 1907, George H. Whipple reported the clinical manifestations and autopsy findings for a patient with the disease that now bears his name [1]. Nearly all of the cardinal clinical manifestations of this disorder—including arthralgias, abdominal pain, fever, diarrhea, malabsorption, weight loss, and cough—were evident in this first patient reported. On the basis of observations of fat and fatty-acid deposits in the intestinal mucosa and mesenteric lymph nodes, Whipple termed the disease " intestinal lipodystrophy " and concluded that the subject of his case report suffered from a disorder of lipid metabolism. However, he did note small bacteria in silver-stained sections of mesenteric lymph nodes. Whipple made no mention of neurologic manifestations, and no post-mortem examination of the central nervous system (CNS) was performed, yet it is now apparent that the CNS is a major site of involvement in extraintestinal Whipple disease (WD) [2, 3] (see below). WD is a rare, chronic, and systemic illness characterized predominantly by intestinal involvement but including a variety of other organs, especially the lym-phatic system, heart, and CNS [2]. It occurs predominantly in middle-aged men. Of 664 patients reviewed by Dobbins, men accounted for 86% of cases, with a mean age of 49 years [2]. The epidemiologic characteristics of WD of the CNS appear to be similar, although in 1 report there was no gender bias [4]. It is possible that CNS involvement reflects a different subset of patients, but this is unknown at present. WD appears to be very rare in children. Farmers are overrepresented among patients with this disorder [2]. WD is an infectious disease. As noted above, Whipple himself observed bacilli-form bodies in involved tissues. Earlier studies had suggested a bacterial etiology, both because successful antibiotic treatment had been reported in 1952 [5] and because detection, by electron microscopy, of numerous small, uniform bacteria in involved tissues had been reported in 1961 [6, 7]. During the early 1990s, amplification of phylogenetically useful genetic sequences of microorganisms by techniques using 16S rRNA identified a unique bacterial 16S rDNA gene sequence in WD tissues [8, 9]. In addition, intact bacilli disappear with clinical response to antibiotics yet reappear during clinical relapse [10]. The WD bacillus has unusual morphology but appears to be monomorphic and undergoes binary fission in affected tissues. The bacillus is rod shaped, measures ∼0.2 mm ϫ 1.2 mm, and is surrounded by a 20-nm-thick cell wall. The outermost layer of …