Isolated CNS W hipple disease with normal brain MRI and false‐positive CSF 14‐3‐3 protein: a case report and review of the literature

Victor W Sung,Khurram Bashir,Kenneth B Fallon,Michael J Lyerly

doi:10.1002/brb3.97

Abstract

Whipple disease (WD) is usually a systemic infectious disease that can have central nervous system (CNS) involvement. WD confined to the CNS is extremely rare and difficult to diagnose, but can be fatal if not treated in a timely fashion. We present the case of a 42-year-old man with a subacute dementia accompanied by a movement disorder consisting of progressive supranuclear gaze palsy, myoclonus, and ataxia. Our patient lacked the typical magnetic resonance imaging (MRI) findings reported with isolated CNS WD and had a false-positive cerebrospinal fluid (CSF) 14-3-3 protein. The patient expired, and definitive diagnosis of isolated CNS WD was made by autopsy with characteristic macrophage accumulations found in the brain but not in the gastrointestinal tract. We examine the literature on isolated CNS WD and discuss how these previously unreported findings make a rare diagnosis even more challenging. The reported patient is the first in the literature with tissue diagnosis of isolated CNS WD in the setting of normal brain MRI and positive CSF 14-3-3 protein. Isolated CNS WD should be added to the list of considerations for a false-positive CSF 14-3-3 protein. Even in the absence of typical MRI lesions, a patient with subacute progressive dementia, supranuclear gaze palsy, and other various neurologic abnormalities should have the diagnosis of isolated CNS WD considered.

Highlights

Whipple disease (WD) is a rare infectious disease caused by the Gram-positive bacillus Tropheryma whipplei that most commonly affects the gastrointestinal system with symptoms of chronic diarrhea and malabsorption but can affect many other organ systems (Dobbins and Ruffin 1967; La Scola et al 2001; Fenollar et al 2007)
In even more rare cases (21 reported), the infectious disease is confined to the central nervous system (CNS) only, with no systemic manifestations, in what is known as isolated CNS WD (Panegyres et al 2006; Marth 2009; Black et al 2010)
As the patient lacked the other supportive features for Creutzfeldt– Jakob disease (CJD) such as characteristic magnetic resonance imaging (MRI) and EEG, we considered the 14-3-3 result to be false positive for CJD, and the patient was discharged to a skilled nursing facility with a presumed degenerative disorder such as a Parkinsonplus syndrome but without a definitive diagnosis

Summary

Introduction

Whipple disease (WD) is a rare infectious disease caused by the Gram-positive bacillus Tropheryma whipplei that most commonly affects the gastrointestinal system with symptoms of chronic diarrhea and malabsorption but can affect many other organ systems (Dobbins and Ruffin 1967; La Scola et al 2001; Fenollar et al 2007). The absence of gastrointestinal and systemic symptoms makes isolated CNS WD difficult to diagnose, and WD is invariably fatal without timely treatment (Keinath et al 1985; Feurle and Marth 1994; Marth 2001; Panegyres et al 2006; Schneider et al 2008).

Results

Conclusion