The neurologic manifestations most often take the form of a slowly progressive memory loss or dementia of subacute or early chronic evolution. Supranuclear ophthalmoplegia, ataxia, seizures, myoclonus, nystagmus, and a highly characteristic movement described as oculomasticatory myorhythmia (which looks to us like rhythmic myoclonus) have been noted less often than the dementing syndrome. The rhythmic myoclonus or spasm occurs in synchronous bursts involving several adjacent regions, mainly the eyes, jaw, and face. This movement disorder is fairly specific but insensitive for Whipple disease, occurring in only approximately 10 percent of patients. As pointed out by Matthews and colleagues, cerebellar ataxia, although obviously much less specific for Whipple disease of the brain, is more frequent, occurring in about half the documented cases. Almost always, the myorhythmias are accompanied by a supranuclear vertical gaze paresis that sometimes affects horizontal eye movements as well. Presumably, the neurologic complications are the result of infiltration of the brain by the organism, but this has not been satisfactorily established.
Approximately half of the patients have a mild pleocytosis and some of these have PAS-positive material in the CSF. A variety of brain imaging abnormalities have been recorded, none characteristic, but either enhancing focal lesions or a normal scan may be found. The diagnosis is made mainly from PAS staining of an intestinal (jejunal) biopsy, as already mentioned, supplemented by PCR testing of the bowel tissue or biopsy material from brain or lymph node. In cases of subacute progressive limb and gait ataxia occurring in middle-aged or older men in whom no cause is uncovered by less-invasive means, it is justifiable to perform these tests (see Chap. 5). Rarely, the neurologic symptoms may occur in the absence of gastrointestinal disease (Adams et al, 1987). In the review of 84 cases of cerebral Whipple disease by Louis and colleagues, 71 percent had cognitive changes, half with psychiatric features; 31 percent had myoclonus; 18 percent had ataxia; and 20 percent had the oculomasticatory and skeletal myorhythmias (Schwartz et al).
Treatment A course of induction by penicillin or ceftriaxone for 2 weeks followed by trimethoprim- sulfamethoxazole or doxycycline continued for 1 year are the currently recommended regimens. An alternative approach is 2 weeks of ceftriaxone followed by treatment with trimethoprim-sulfamethoxazole or a tetracycline for a year. Antibiotic-resistant cases and instances of relapse after antibiotic treatment are known. The review by Anderson may be consulted for details.