Isolated CNS Whipple disease with normal brain MRI and false-positive CSF 14-3-3 protein: A case report and review of the literature

Academic Article


  • 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. Isolated CNS WD, while rare, is important to recognize as it may be treatable and when missed can be fatal. We review the literature regarding isolated CNS WD and use our case to illustrate that the suspicion for isolated CNS WD should remain high even in the absence of commonly described features such as abnormal hyperintense lesions on MRI. Our case also had a false-positive CSF 14-3-3 protein, and therefore, isolated CNS WD should be considered in those cases as well. © 2012 The Authors.
  • Published In

  • Brain and Behavior  Journal
  • Digital Object Identifier (doi)

    Author List

  • Sung VW; Lyerly MJ; Fallon KB; Bashir K
  • Start Page

  • 838
  • End Page

  • 843
  • Volume

  • 2
  • Issue

  • 6