Progressive dementia associated with ataxia or obesity in patients with Tropheryma whipplei encephalitis

Abstract

BackgroundTropheryma whipplei, the agent of Whipple's disease, causes localised infections in the absence of histological digestive involvement. Our objective is to describe T. whipplei encephalitis.MethodsWe first diagnosed a patient presenting dementia and obesity whose brain biopsy and cerebrospinal fluid specimens contained T. whipplei DNA and who responded dramatically to antibiotic treatment. We subsequently tested cerebrospinal fluid specimens and brain biopsies sent to our laboratory using T. whipplei PCR assays. PAS-staining and T. whipplei immunohistochemistry were also performed on brain biopsies. Analysis was conducted for 824 cerebrospinal fluid specimens and 16 brain biopsies.ResultsWe diagnosed seven patients with T. whipplei encephalitis who demonstrated no digestive involvement. Detailed clinical histories were available for 5 of them. Regular PCR that targeted a monocopy sequence, PAS-staining and immunohistochemistry were negative; however, several highly sensitive and specific PCR assays targeting a repeated sequence were positive. Cognitive impairments and ataxia were the most common neurologic manifestations. Weight gain was paradoxically observed for 2 patients. The patients' responses to the antibiotic treatment were dramatic and included weight loss in the obese patients.ConclusionsWe describe a new clinical condition in patients with dementia and obesity or ataxia linked to T. whipplei that may be cured with antibiotics.

Clinical Manifestations, Treatment, and Diagnosis of Tropheryma whipplei Infections

“…The most common neurological symptoms are cognitive impairment, ataxia, and supranuclear ophthalmoplegia (157). A study from 2011 showed that ataxia and dementia were more severe in patients with encephalitis than in patients with classic Whipple's disease, making early recognition clinically important (157). Recently, a paradoxical association between T. whipplei encephalitis (as was documented by brain biopsy specimen) and obesity has been found in several cases (157).…”

“…A study from 2011 showed that ataxia and dementia were more severe in patients with encephalitis than in patients with classic Whipple's disease, making early recognition clinically important (157). Recently, a paradoxical association between T. whipplei encephalitis (as was documented by brain biopsy specimen) and obesity has been found in several cases (157). These patients suffered from unexplained progressive dementia that was in most cases associated with ataxia and recent obesity.…”

“…Several studies by a French group reported the clinical implications of isolated encephalitis caused by T. whipplei (127,157,158). The most common neurological symptoms are cognitive impairment, ataxia, and supranuclear ophthalmoplegia (157).…”

“…Several studies by a French group reported the clinical implications of isolated encephalitis caused by T. whipplei (127,157,158). The most common neurological symptoms are cognitive impairment, ataxia, and supranuclear ophthalmoplegia (157). A study from 2011 showed that ataxia and dementia were more severe in patients with encephalitis than in patients with classic Whipple's disease, making early recognition clinically important (157).…”

“…The combination of cerebellar syndromes, dementia, and obesity should therefore trigger physicians to consider a T. whipplei infection. Definite diagnosis is complicated, as it would involve obtaining brain biopsy specimens, but since empirical treatment was reported to rapidly resolve the clinical symptoms, one might consider starting treatment even in the absence of a final diagnosis (157).…”