Neurologic presentation of Whipple disease: report of 12 cases and review of the literature

Medicine (Baltimore). 2002 Nov;81(6):443-57. doi: 10.1097/00005792-200211000-00005.


We report 12 cases of Whipple disease in patients with prominent neurologic symptoms, along with 122 cases of Whipple disease with nervous system involvement reported in the literature. We analyzed the clinical signs and results of additional examinations in 2 groups: the first group included patients with predominantly but not exclusively neurologic signs, and the second included patients with clinically isolated neurologic presentation of the disease. Whipple disease is a multisystemic infectious disease due to Tropheryma whippelii that may present with prominent or isolated symptoms of either the central or the peripheral nervous system. Recent reports stress the importance of polymerase chain reaction (PCR) analysis of cerebrospinal fluid, magnetic resonance imaging (MRI) during follow-up, and prolonged antibiotic therapy with drugs able to cross the blood-brain barrier. Cerebrospinal fluid should be analyzed repeatedly during follow-up, and treatment should be discontinued only when the results of PCR assay performed on cerebrospinal fluid are negative. Other examinations to be done include searching for gastrointestinal tract involvement with multiple duodenal biopsies and searching for systemic involvement with lymph node biopsies, which should be analyzed with light microscopy, electron microscopy, and PCR. When all examinations are negative, if Whipple disease is suspected and a lesion is found on brain MRI, a stereotactic cerebral biopsy should be performed. Treating Whipple disease with long-term trimethoprim-sulfamethoxazole is usually effective, but the use of third-generation cephalosporins in case of incomplete response deserves further attention.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Actinomycetales Infections / complications*
  • Actinomycetales Infections / microbiology
  • Adult
  • Aged
  • Anti-Bacterial Agents / therapeutic use
  • Anti-Infective Agents / therapeutic use
  • Biopsy
  • Blood-Brain Barrier
  • Central Nervous System Diseases / diagnosis
  • Central Nervous System Diseases / drug therapy
  • Central Nervous System Diseases / microbiology*
  • Cephalosporins / therapeutic use
  • Female
  • Humans
  • Lymph Nodes / pathology
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Peripheral Nervous System Diseases / diagnosis
  • Peripheral Nervous System Diseases / drug therapy
  • Peripheral Nervous System Diseases / microbiology*
  • Polymerase Chain Reaction
  • Stereotaxic Techniques
  • Treatment Outcome
  • Trimethoprim, Sulfamethoxazole Drug Combination / therapeutic use
  • Whipple Disease / complications*
  • Whipple Disease / microbiology


  • Anti-Bacterial Agents
  • Anti-Infective Agents
  • Cephalosporins
  • Trimethoprim, Sulfamethoxazole Drug Combination