CNS Whipple's disease factsheet

The topic of CNS Whipple’s disease came up in a recent email exchange, so I thought I’d share with you a fact sheet on the disease:

DESCRIPTION:

First described by George Whipple in 1907, Whipple disease is a multisystem disorder that usually includes the intestinal tract. The causative organism is a Gram-positive actinomycete called Tropheryma whippleii.

EPIDEMIOLOGY:

Interestingly, Whipple’s disease occurs about six times more commonly in men than in women. The disease tends to occur in late middle age.

CLINICAL PRESENTATION:

Most patients present with such symptoms as arthralgia, weight loss, steatorrhea, lymphadenopathy, and hyperpigmentation. Some patients develop neurological disease, usually in combination with systemic symptoms. The most common neurologic manifestations are dementia, ophthalmoplegia, hypothalamopituitary dysfunction, and myoclonus. Occulofacial-skeletal myorhythmia is particularly suggestive of Whipple’s disease. Only rarely is Whipple’s disease confined exclusively to the central nervous system.

PATHOLOGIC DIAGNOSIS:

Intestinal biopsy: The diagnosis is usually made by jejunal biopsy, which demonstrates the characteristic macrophages containing PAS-positive rod-shaped structures, termed sickle particle containing (SPC) cells. This microscopic finding may be present even in patients without clinically apparent intestinal involvement. PCR-based assays of intestinal tissue may allow the confirmation of suspected CNS Whipple’s disease, even when histology is not revealing. In patients with neurological manifestations, SPC cells may rarely be found in the CSF.

Brain biopsy: Exceptionally, brain biopsy is required to establish the diagnosis; however, PCR analysis of CSF or synovial fluid allows the diagnosis to be made in most instances. Microscopically, accumulation of macrophages is seen, often with a perivascular distribution, surrounded by a lymphocytic and plasma cell inflammatory reaction of variable intensity, and gliotic brain tissue containing hypertrophied astrocytes. Macrophages with lipid-filled cytoplasm containing sickle-shaped inclusions that are PAS-positive are seen [see figure]. The organisms, which are also Gram-positive and methenamine silver-positive, can also be seen free within the tissue.

DISEASE DISTRIBUTION WITHIN THE CNS

The pathology is usually characterized by small lesions disseminated throughout the entire CNS but especially abundant in the cortex. Larger intracerebral pseudo-tumors are uncommon. Leptomeningeal involvement is occasionally complicated by tiny infarcts scattered throughout the brain; and first presentation as a multiple stroke syndrome has been reported.

REFERENCE:

Greenfield’s Neuropathology (8^th edition), Love S, Louis DN, and Ellison DW (eds). Edward Arnold Publishers (2008). Chapter 18: Bacterial Infections, by Brown E. and Gray F. pages 1426-7.