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BMC Infectious Diseases
Published in: BMC Infectious Diseases 1/2011

Open Access 01-12-2011 | Research article

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

Authors: Florence Fenollar, François Nicoli, Claire Paquet, Hubert Lepidi, Patrick Cozzone, Jean-Christophe Antoine, Jean Pouget, Didier Raoult

Published in: BMC Infectious Diseases | Issue 1/2011

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Abstract

Background

Tropheryma 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.

Methods

We 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.

Results

We 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.

Conclusions

We describe a new clinical condition in patients with dementia and obesity or ataxia linked to T. whipplei that may be cured with antibiotics.
Appendix
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Literature
1.
Fenollar F, Puéchal X, Raoult D: Whipple's disease. New Engl J Med. 2007, 356: 55-66. 10.1056/NEJMra062477.CrossRefPubMed
2.
Whipple GH: A hitherto undescribed disease characterised anatomically by deposits of fat and fatty acids in the intestinal and mesenteric lymphatic tissues. Bull Johns Hopkins Hosp. 1907, 18: 382-391.
3.
Paulley JW: A case of Whipple's disease (intestinal lipodystrophy). Gastroenterology. 1952, 22: 128-133.PubMed
4.
Wilson KH, Blitchington R, Frothingham R, Wilson JA: Phylogeny of the Whipple's disease-associated bacterium. Lancet. 1991, 338: 474-475. 10.1016/0140-6736(91)90545-Z.CrossRefPubMed
5.
Raoult D, Birg M, La Scola B, Fournier P, Enea M, Lepidi H, et al: Cultivation of the bacillus of Whipple's disease. N Engl J Med. 2000, 342: 620-625. 10.1056/NEJM200003023420903.CrossRefPubMed
6.
Gubler JG, Kuster M, Dutly F, Bannwart F, Krause M, Vögelin HP, et al: Whipple endocarditis without overt gastrointestinal disease: Report of four cases. Ann Intern Med. 1999, 131: 112-116.CrossRefPubMed
7.
Rickman LS, Freeman WR, Green WR, Feldman ST, Sullivan J, Russack V, et al: Uveitis caused by Tropheryma whippelii (Whipple's bacillus). N Engl J Med. 1995, 332: 363-366. 10.1056/NEJM199502093320604.CrossRefPubMed
8.
Drancourt M, Fenollar F, Denis D, Raoult D: Postoperative panophthalmitis caused by Whipple disease. Emerg Infect Dis. 2009, 15: 825-827. 10.3201/eid1505.081209.CrossRefPubMedPubMedCentral
9.
Lagier JC, Lepidi H, Raoult D, Fenollar F: Clinical presentation of 142 patients with systemic Tropheryma whipplei infections diagnosed or confirmed in a reference center. Medicine (Baltimore). 2010, 89: 337-345. 10.1097/MD.0b013e3181f204a8.CrossRef
10.
Fenollar F, Raoult D: How should classic Whipple's disease be managed?. Nat Rev Gastroenterol Hepatol. 2010, 7: 246-248. 10.1038/nrgastro.2010.46.CrossRefPubMed
11.
Harris JK, De Groote MA, Sagel SD, Zemanick ET, Kapsner R, Penvari C, et al: Molecular identification of bacteria in bronchoalveolar lavage fluid from children with cystic fibrosis. Proc Natl Acad Sci USA. 2007, 104: 20529-20533. 10.1073/pnas.0709804104.CrossRefPubMedPubMedCentral
12.
Bousbia S, Papazian L, Auffray JP, Fenollar F, Martin C, Li W, et al: Molecular analysis of bronchoalveolar lavage in patients with pneumonia reveals the presence of Tropheryma whipplei. Emerg Infect Dis. 2010, 16: 258-263.CrossRefPubMedPubMedCentral
13.
Raoult D, Fenollar F, Rolain JM, Minodier P, Bosdure E, Li W, et al: Tropheryma whipplei is commonly associated to gastroenteritis in young children. Emerg Infect Dis. 2010, 16: 776-782.CrossRefPubMedPubMedCentral
14.
Fenollar F, Mediannikov O, Socolovschi C, Bassene H, Diatta G, Richet H, et al: Tropheryma whipplei bacteremia during fever in rural West Africa. Clin Infect Dis. 2010, 51: 515-521. 10.1086/655677.CrossRefPubMed
15.
Gerard A, Sarrot-Reynauld F, Liozon E, Cathébras P, Besson G, Robin C, et al: Neurologic presentation of Whipple disease: report of 12 cases and review of the literature. Medicine (Baltimore). 2002, 81: 443-457. 10.1097/00005792-200211000-00005.CrossRef
16.
Fenollar F, Fournier PE, Robert C, Raoult D: Use of genome selected repeated sequences increases the sensitivity of PCR detection of Tropheryma whipplei. J Clin Microbiol. 2004, 42: 401-403. 10.1128/JCM.42.1.401-403.2004.CrossRefPubMedPubMedCentral
17.
Fenollar F, Fournier PE, Raoult D, Gerolami R, Lepidi H, Poyart C: Quantitative detection of Tropheryma whipplei DNA by real-time PCR. J Clin Microbiol. 2002, 40: 1119-1120. 10.1128/JCM.40.3.1119-1120.2002.CrossRefPubMedPubMedCentral
18.
Fenollar F, Laouira S, Lepidi H, Rolain J, Raoult D: Value of Tropheryma whipplei quantitative PCR assay for the diagnosis of Whipple's disease - usefulness of saliva and stool specimens for first line screening. Clin Infect Dis. 2008, 47: 659-667. 10.1086/590559.CrossRefPubMed
19.
La Scola B, Fenollar F, Fournier PE, Altwegg M, Mallet MN, Raoult D: Description of Tropheryma whipplei gen. nov., sp. nov., the Whipple's disease bacillus. Int J Syst Evol Microbiol. 2001, 51: 1471-1479.CrossRefPubMed
20.
Rolain JM, Fenollar F, Raoult D: False positive PCR detection of Tropheryma whipplei in the saliva of healthy people. BMC Microbiol. 2007, 7: 48-10.1186/1471-2180-7-48.CrossRefPubMedPubMedCentral
21.
Fenollar F, Trani M, Davoust B, Salle B, Birg ML, Rolain JM, et al: Carriage of Tropheryma whipplei in stools of sewer workers and human controls, but not in monkeys and apes. J Infect Dis. 2008, 197: 880-887. 10.1086/528693.CrossRefPubMed
22.
Raoult D, Fenollar F, Birg ML: Culture of Tropheryma whipplei from the stool of a patient with Whipple's disease. N Engl J Med. 2006, 355: 1503-1505. 10.1056/NEJMc061049.CrossRefPubMed
23.
Fenollar F, Amphoux B, Raoult D: A paradoxical Tropheryma whipplei western blot differentiates patients with Whipple's disease from asymptomatic carriers. Clin Infect Dis. 2009, 49: 717-723. 10.1086/604717.CrossRefPubMed
24.
Fenollar F, Birg ML, Gauduchon V, Raoult D: Culture of Tropheryma whipplei from human samples: A 3-year experience (1999 to 2002). J Clin Microbiol. 2004, 41: 3816-3822.CrossRef
25.
Renesto P, Crapoulet N, Ogata H, La Scola B, Vestris G, Claverie JM, et al: Genome-based design of a cell-free culture medium for Tropheryma whipplei. Lancet. 2003, 362: 447-449. 10.1016/S0140-6736(03)14071-8.CrossRefPubMed
26.
Galanaud D, Nicoli F, Le Fur Y, Guye M, Ranjeva JP, Confort-Gouny S, et al: Multimodal magnetic resonance imaging of the central nervous system. Biochimie. 2003, 85: 905-914. 10.1016/j.biochi.2003.09.014.CrossRefPubMed
27.
Louis ED, Lynch T, Kaufmann P, Fahn S, Odel J: Diagnostic guidelines in central nervous system Whipple's disease. Ann Neurol. 1996, 40: 561-568. 10.1002/ana.410400404.CrossRefPubMed
28.
Coria F, Cuadrado N, Velasco C, Jiménez Carmena JJ, Jiménez MI, Mena FJ, et al: Whipple's disease with isolated central nervous system symtomatology diagnosed by molecular identification of Tropheryma whippelii in peripheral blood. Neurologia. 2000, 15: 173-176.PubMed
29.
von Herbay A, Ditton HJ, Schuhmacher F, Maiwald M: Whipple's disease: staging and monitoring by cytology and polymerase chain reaction analysis of cerebral fluid. Gastroenterology. 1997, 113: 434-441. 10.1053/gast.1997.v113.pm9247461.CrossRefPubMed
30.
Rossi T, Haghighipour M, Haghighi M, Paolini S, Scarpino O: Cerebral Whipple's disease as a cause of reversible dementia. Clin Neurol Neurosurg. 2005, 107: 258-261. 10.1016/j.clineuro.2004.10.014.CrossRefPubMed
31.
Averbuch-Heller L, Paulson G, Daroff R, Leight J: Whipple's disease mimicking progressive supranuclear palsy: the diagnostic value of eye movement recording. J Neurol Neurosurg Psychiatry. 1999, 66: 532-535. 10.1136/jnnp.66.4.532.CrossRefPubMedPubMedCentral
32.
Halperin J, Landis D, Kleinman G: Whipple disease of the nervous system. Neurology. 1982, 32: 612-617.CrossRefPubMed
33.
Brown A, Lane J, Murayama S, Vollmer D: Whipple's disease presenting with isolated neurological symptoms. J Neurosurg. 1990, 73: 623-627. 10.3171/jns.1990.73.4.0623.CrossRefPubMed
34.
Nelson JW, White ML, Zhang Y, Moritani T: Proton magnetic resonance spectroscopy and diffusion-weighted imaging of central nervous system Whipple disease. J Comput Assist Tomogr. 2005, 29: 320-322. 10.1097/01.rct.0000163570.71758.92.CrossRefPubMed
35.
Henning S, Tings T, Schmidt H, Tergau F, Wolf S, Scholz K, et al: A case of cerebral Whipple's disease initially presenting with isolated focal myoclonus. Eur J Neurol. 2006, 13: 659-661. 10.1111/j.1468-1331.2006.01396.x.CrossRefPubMed
36.
Panegyres PK, Edis R, Beaman M, Fallon M: Primary Whipple's disease of the brain: characterisation of the clinical syndrome and molecular diagnosis. QJM. 2006, 99: 609-623. 10.1093/qjmed/hcl081.CrossRefPubMed
37.
Lee AG: Whipple disease with supranuclear ophtalmoplegia diagnosed by polymerase chain reaction of cerebrospinal fluid. J Neuroophtamol. 2002, 22: 18-21.CrossRef
38.
Romanul F, Radvany J, Rosales R: Whipple's disease confined to the brain: a case studied clinically and pathologically. J Neurol Neurosurg Psychiatry. 1977, 40: 901-909. 10.1136/jnnp.40.9.901.CrossRefPubMedPubMedCentral
39.
Wroe S, Pires M, Harding B, Youl B, Shorvon S: Whipple's disease confined to the CNS presenting with multiple intracerebral mass lesions. J Neurol Neurosurg Psychiatry. 1991, 54: 989-992. 10.1136/jnnp.54.11.989.CrossRefPubMedPubMedCentral
40.
Posada IJ, Ferreiro-Sieiro A, Lopez-Valdes E, Cabello A, Bermejo-Pareja F: Whipple's disease confined to the brain. A clinical case with pathological confirmation at necropsy. Rev Neurol. 2004, 38: 196-198.PubMed
41.
Adams M, Rhyner P, Day J, DeArmond S, Smuckler E: Whipple's disease confined to the central nervous system. Ann Neurol. 1987, 21: 104-108. 10.1002/ana.410210121.CrossRefPubMed
42.
Schwartz M, Selhorst J, Ochs A, Beck R, Campbell W, Harris J, et al: Oculomasticatory myorhythmia: a unique movement disorder occurring in Whipple's disease. Ann Neurol. 1986, 20: 677-683. 10.1002/ana.410200605.CrossRefPubMed
43.
Peters G, du Plessis DG, Humphrey PR: Cerebral Whipple's disease with a stroke-like presentation and cerebrovascular pathology. J Neurol Neurosurg Psychiatry. 2002, 73: 336-339. 10.1136/jnnp.73.3.336.CrossRefPubMedPubMedCentral
44.
Dobbins WO: Whipple's disease. Thomas Books. 1987, Springfield, IL
45.
Bernachon E, Laxenaire N, Le Baleur Y, Miquel J, Bernachon-Agache F, Gillot JM: La curiosité est un joli défaut. Rev Med Int. 2003, 25: 157-159.CrossRef
46.
Codden T, Lenaerts A, Chaikh A, Henry JP: Whipple disease revealed by weight loss and neurologic signs. Gastroenterol Clin Biol. 2003, 27: 834-836.PubMed
47.
Dhote R, Mir O, Moulin V, Ropert S, Permal S, Scavennec R, et al: Un glissement trop fébrile. Rev Med Int. 2003, 24 (Suppl 2): 259-260.CrossRef
48.
Levy S, Degott C, Redondo A, Benhamou JP, Bernuau J: Acute intracranial hypertension and anicteric cholestasis revealing Whipple's disease without digestive involvement. Gastroenterol Clin Biol. 2001, 25: 100-102.PubMed
49.
Matthews BR, Jones LK, Saad DA, Aksamit AJ, Josephs KA: Cerebellar ataxia and central nervous system Whipple disease. Arch Neurol. 2005, 62: 618-620. 10.1001/archneur.62.4.618.CrossRefPubMed
50.
Reyes MC, Cordero FC, Torronteras SR, Reina Campos FR, Marquez Galan JL, Sanchez AM: Whipple's disease: report of cases diagnosed in our hospital. Rev Esp Enferm Dig. 2003, 95: 149-8.
51.
Pruss H, Katchanov J, Zschenderlein R, Loddenkemper C, Schneider T, Moos V: A patient with cerebral Whipple's disease with gastric involvement but no gastrointestinal symptoms - a consequence of local protective immunity?. J Neurol Neurosurg Psychiatry. 2007, 78: 896-898. 10.1136/jnnp.2006.110908.CrossRefPubMedPubMedCentral
52.
Maia LF, Marta M, Lopes V, Rocha N, Lopes C, Martins-da-Silva A, et al: Hypersomnia in Whipple disease: case report. Arq Neuropsiquiatr. 2006, 64: 865-868. 10.1590/S0004-282X2006000500030.CrossRefPubMed
53.
Magherini A, Pentore R, Grandi M, Leone ME, Nichelli PF: Progressive supranuclear gaze palsy without parkinsonism: a case of neuro-Whipple. Parkinsonism Relat Disord. 2007, 13: 449-452. 10.1016/j.parkreldis.2006.05.035.CrossRefPubMed
54.
Famularo G, Minisola G, De SC: A patient with cerebral Whipple's disease and a stroke-like syndrome. Scand J Gastroenterol. 2005, 40: 607-609. 10.1080/00365520510015494.CrossRefPubMed
55.
Angelakis E, Fenollar F, Lepidi H, Birg ML, Raoult D: Tropheryma whipplei in the skin of patients with classic Whipple's disease. J Infect. 2010, 61: 266-269. 10.1016/j.jinf.2010.06.007.CrossRefPubMed
56.
Vasilakopoulou A, le Roux CW: Could a virus contribute to weight gain?. Int J Obes (Lond). 2007, 31: 1350-1356. 10.1038/sj.ijo.0803623.CrossRef
57.
58.
Goyo D, Camacho A, Gomez C, de Las Heras RS, Otero JR, Chaves F: False-positive PCR detection of Tropheryma whipplei in cerebrospinal fluid and biopsy samples from a child with chronic lymphocytic meningitis. J Clin Microbiol. 2009, 47: 3783-3784. 10.1128/JCM.00927-09.CrossRefPubMedPubMedCentral
59.
Müller SA, Vogt P, Altwegg M, Seebach JD: Deadly carousel or difficult interpretation of new diagnostic tools for Whipple's disease: case report and review of the literature. Infection. 2005, 33: 39-42. 10.1007/s15010-005-4067-7.CrossRefPubMed
60.
Ghigo E, Capo C, Aurouze M, Tung CH, Gorvel JP, Raoult D, et al: Survival of Tropheryma whipplei, the agent of Whipple's disease, requires phagosome acidification. Infect Immun. 2002, 70: 1501-1506. 10.1128/IAI.70.3.1501-1506.2002.CrossRefPubMedPubMedCentral
61.
Lagier JC, Fenollar F, Lepidi H, Raoult D: Failure and relapse after treatment with Trimethoprim-Sulfamethoxazole in classic Whipple's disease. J Antimicrob Chemother. 2010, 65: 2005-2012. 10.1093/jac/dkq263.CrossRefPubMed
Metadata
Title
Progressive dementia associated with ataxia or obesity in patients with Tropheryma whipplei encephalitis
Authors
Florence Fenollar
François Nicoli
Claire Paquet
Hubert Lepidi
Patrick Cozzone
Jean-Christophe Antoine
Jean Pouget
Didier Raoult
Publication date
01-12-2011
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2011
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/1471-2334-11-171

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