Polymerase chain reaction—based detection of <i>Tropheryma whippelii</i> in central nervous system Whipple's disease

Lynch, Tim; Odel, Jeffrey G.; Fredericks, Doral; Louis, Elan D.; Forman, Stephen J.; Rotterdam, Heidrun; Fahn, Stanley; Relman, David A.

doi:10.1002/ana.410420120

Cited by 48 publications

(35 citation statements)

References 12 publications

(1 reference statement)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Also, while the sensitivity of PCR for WD in the CSF and serum is high, the exact negative predictive value of PCR is not known. 20,21 A negative PCR result or negative finding on small bowel biopsy histology do not completely exclude the diagnosis; thus, a complete work-up requires MR imaging, PCRs, and a small bowel biopsy in addition to a careful history and physical examination.…”

Section: Discussionmentioning

confidence: 99%

MR Imaging of Central Nervous System Whipple Disease: A 15-Year Review

Black

Aksamit²,

Morris

2010

AJNR Am J Neuroradiol

View full text Add to dashboard Cite

SUMMARY: CNS WD is fatal if antibiotics are not begun early, but knowledge regarding the variety of presentations on MR imaging is limited. In order to more effectively recognize this entity on MR imaging, the Mayo Clinic medical records were reviewed for subjects diagnosed with CNS WD from 1992-2006 who had also undergone MR imaging of the neuraxis. Seven subjects were identified and their imaging findings were reviewed by the authors. Four of 7 had head MR imaging findings indicative of WD. Two subjects demonstrated high T2 signal within the corticospinal tracts. CNS WD may demonstrate high T2 signal with minimal enhancement and no restricted diffusion, primarily in the midline of the midbrain, hypothalamus, and mesial temporal lobes and occasionally the corticospinal tracts. MR imaging may also be normal. Radiologists should be aware of these presentations and be prepared to mention CNS WD as a diagnostic possibility since early antibiotic therapy may significantly impact morbidity and mortality.ABBREVIATIONS: asxs ϭ asymptomatic; CNS ϭ central nervous system; FLAIR ϭ fluid-attenuated inversion recovery; GI ϭ gastrointestinal; NP ϭ not performed; PAS ϭ periodic-acid-Schiff; PCR ϭ polymerase chain reaction; Rx ϭ therapy; WD ϭ Whipple disease W D is a rare disorder that was first described in 1907 and subsequently found to be caused by a bacterium. Although WD is a systemic illness, it may present with signs and symptoms isolated to gastrointestinal, cardiac, or central nervous systems.1 Approximately 33% of patients with WD experience neurologic symptoms, including encephalopathy, ophthalmoplegia, myoclonus, ataxia, upper motor neuron signs, and hypothalamic manifestations, among others.WD is invariably fatal without treatment, but even with antibiotics, 2%-33% of patients relapse, most often with a neurologic manifestation.2 CNS involvement of WD carries a grim prognosis with approximately 25% of patients dying within 4 years of diagnosis and another 25% having major neurologic sequelae.3 Approximately 60% of patients with CNS WD experience some improvement in their symptoms during antibiotic therapy; thus, early diagnosis and treatment initiation are paramount for survival.1 Diagnostic efforts may be hampered by the plethora of presenting signs and symptoms as well as the lack of sensitivity and specificity of laboratory tests.CNS WD is a subset of a rare disease. Only approximately 1000 cases of all types of WD have been reported, and our understanding of head MR imaging findings is based only on case reports; thus, each new case imaged with modern equipment has the potential to expand our understanding significantly as long as the diagnosis has been carefully established. Materials and MethodsThis retrospective study was approved by the Mayo Clinic institutional review board. The Mayo Clinic medical records from 1992 to 2006 were searched for terms including "Whipple disease" and "encephalopathy." Review of an initial 140 subjects identified with some form of WD revealed 20 patients thought to have CNS WD....

show abstract

Section: Discussionmentioning

confidence: 99%

MR Imaging of Central Nervous System Whipple Disease: A 15-Year Review

Black

Aksamit²,

Morris

2010

AJNR Am J Neuroradiol

View full text Add to dashboard Cite

show abstract

“…The clinical features of CNS disease are diverse, as Whipple's disease may aVect the brain stem, the diencephalon (epithalamus, subthalamus, and hypothalamus), the rhinencephalon (that part of the cerebral hemisphere directly related to the sense of smell), the medial temporal lobe, 9 and the meninges. 13 42 Confusional states, coma, and brain stem syndromes, seizures, cerebellar ataxia, and myelopathy are common features.…”

Section: Musculoskeletal Systemmentioning

confidence: 99%

“…9 46 50 51 Oculofacial-skeletal myorhythmia has also been described: a slow smooth convergent-divergent pendular nystagmus associated with synchronous contractions of other body parts. [52][53][54] These signs occur in 20% of patients with CNS disease and are always associated with a supranuclear vertical gaze palsy.…”

Section: Musculoskeletal Systemmentioning

confidence: 99%

“…10 26 27 It has been suggested that, clinically, oculofacial-skeletal myorhythmia or oculomasticatory myorhythmia alone establishes the diagnosis of Whipple's disease. 9 Early diagnosis is essential. Whipple's disease is potentially fatal but responds dramatically to antibiotic treatment.…”

Section: The Diagnosismentioning

confidence: 99%

“…These tests may now be unnecessary to establish malabsorption resulting from small bowel pathology, as an endoscopic biopsy can provide the same information. On endoscopy, the findings in 12 patients were: oesophagitis (1), erosive gastritis (4), atrophic gastritis (2), severe erosive bulbitis (3), and pathognomonic postbulbar duodenal lesions (9), and after antibiotic treatment these lesions resolved in 20% within six months, and in all the patients by nine months. 66 However, PAS positive macrophages can persist in endoscopic biopsies for years.…”

Section: The Diagnosismentioning

confidence: 99%

See 2 more Smart Citations

Whipple's disease

Ratnaike

2000

Postgrad Med J

View full text Add to dashboard Cite

Whipple's disease is a systemic bacterial infection and the common though not invariable manifestations are diarrhoea, weight loss, abdominal pain, and arthralgia. Arthritis or arthralgia may be the only presenting symptom, predating other manifestations by years. Virtually all organs in the body may be aVected, with protean clinical manifestations. Various immunological abnormalities, some of which may be epiphenomena, are described. The causative organism is Tropheryma whippelii.The disease is uncommon though lethal if not treated. Recent data suggest the disease occurs in an older age group than previously described. The characteristic histopathological features are found most often in the small intestine. These are variable villous atrophy and distension of the normal villous architecture by an infiltrate of foamy macrophages with a coarsely granular cytoplasm, which stain a brilliant magenta colour with PAS. These pathognomonic PAS positive macrophages may also be present in the peripheral and mesenteric lymph nodes and various other organs. The histological diVerential diagnoses include histoplasmosis and Mycobacterium aviumintercellulare complex.The clinical diagnosis of Whipple's disease may be elusive, especially if gastrointestinal symptoms are not present. A unique sign of CNS involvement, if present, is oculofacial-skeletal myorhythmia or oculomasticatory myorhythmia, both diagnostic of Whipple's disease. A small bowel biopsy is often diagnostic, though in about 30% of patients no abnormality is present. In patients with only CNS involvement, a stereotactic brain biopsy can be done under local anaesthetic. A recent important diagnostic test is polymerase chain reaction of the 16S ribosomal RNA of Tropheryma whippelii.Whipple's disease is potentially fatal but responds dramatically to antibiotic treatment. In this review the current recommended treatments are presented. The response to treatment should be monitored closely, as relapses are common. CNS involvement requires more vigorous treatment because there is a high rate of recurrence after apparently successful treatment. (Postgrad Med J 2000;76:760-766)

show abstract