Primary Whipple's disease of the brain: Characterization of the clinical syndrome and molecular diagnosis

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QJM: monthly journal of the Association of Physicians (Impact Factor: 2.5). 10/2006; 99(9):609-23. DOI: 10.1093/qjmed/hcl081
Source: PubMed


Whipple's disease (WD) of the brain without evidence of systemic involvement is a rare illness that is difficult to recognize and potentially life-threatening.
To elucidate the clinical features and diagnosis of primary WD of the brain.
A single case study, with review of published data.
We linked the information about our patient with 956 citations to published WD material. We were able to identify 19 other patients with primary WD of the brain.
Our patient was a 48-year-old woman who presented 2 years ago with generalized tonic/clonic seizures. WD of the brain was diagnosed after a life-threatening subacute deterioration leading to reduced consciousness and eye movement abnormalities. She had atrophy and gliosis of the right hippocampal formation, and nodular enhanc-ing lesions. She developed the syndrome of inappropriate ADH secretion, blepharospasm with a complete paralysis of vertical gaze, a severe amnesic syndrome, obstructive sleep apnoea, altered sleep physiology and CSF oligoclonal bands. Primary WD of the brain was diagnosed after PCR confirmed Tropheryma whipplei DNA in CSF and blood. She recovered after intravenous methylprednisolone, meropenem and cotrimoxazole. She has now survived for 24 months, lives independently and drives. Comparing our patient with the 19 others, two clinical syndromes were apparent, in both adults and children: (i) multifarious neurological symptoms and signs with a CT or MRI showing multiple nodular enhancing lesions; (ii) focal neurology secondary to solitary mass lesions.
Primary WD of the brain may be diagnosed by recognition of these two clinical syndromes, and confirmed by the application of molecular biological techniques such as PCR.

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Available from: Peter Konstantine Panegyres
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    • "reviewing the literature and presenting 19 patients with primary WD of the brain without systemic involvement (in contrast to our patient) found three patients with negative or inconclusive PCR on CSF [19]. "
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    ABSTRACT: Whipple's disease (WD) is a rare systemic disease caused by the gram-positive bacillus Tropheryma Whipplei and mostly characterized by arthralgias, chronic diarrhea, weight loss, fever and abdominal pain. Central Nervous System involvement is not uncommon and it may precede other disease manifestations, appear after treatment and improvement of gastrointestinal signs or rarely be the only WD symptom. We report a case in a middle-aged male with unexplained neurological signs and symptoms which were presented as relapse of previously undiagnosed WD with atypical symptoms at onset. After diagnosis confirmation, the patient was appropriately treated which resulted in improvement of major symptoms.
    Full-text · Article · Jun 2015 · The Open Neurology Journal
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    • "Sur le plan de l'imagerie, les atteintes neurologiques sont aspécifiques , avec le plus souvent en IRM des hypersignaux en séquence FLAIR et des anomalies de la spectroscopie [5] [7] [8] [14]. Seulement trois cas de patients atteints de maladie de Whipple explorés par PET-scanner cérébral au 18 FDG ont actuellement été rapportés dans la littérature, avec mise en évidence de foyers hypermétaboliques dans les trois cas et un hypométabolisme cortical global dans un des cas [4] [10] [11]. Si le diagnostic de la maladie de Whipple classique est basé sur l'atteinte de l'intestin grêle avec une positivité de la coloration PAS ou de l'immuno-histochimie spécifique [1] [15], le diagnostic des atteintes neurologiques isolées est souvent difficile et le plus souvent basé sur un faisceau d'arguments incluant le plus souvent la positivité d'une PCR ciblant spécifiquement T. whipplei dans le LCR [16]. "
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    ABSTRACT: Whipple's disease is a rare infectious disease due to Tropheryma whipplei, a bacterium rarely causing severe localized neurological infection (only 25 cases reported in the literature), which are more often diagnosed by a positive T. whipplei PCR performed on cerebrospinal fluid. We report the third case of progressive dementia associated with obesity and ataxia in a 52-year-old man. Classic laboratory results performed to identify the etiology of the clinical features were non-contributive: only a saliva T. whipplei PCR was strongly positive and the Western blot serology has detected an asymptomatic carriage profile. The (18)FDG-PET highlighted a frontal area hypometabolism. An antibiotic treatment by doxycycline allowed a partial regression of the neurological manifestations, a weight loss and a significant improvement of the (18)FDG frontal hypometabolism. Progressive dementia associated with ataxia and obesity is a new clinical syndrome caused by T. whipplei. Antibiotic test by doxycycline can help to the diagnosis and (18)-FDG could facilitate the follow-up.
    Full-text · Article · Sep 2013 · La Revue de Médecine Interne
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    • "The current treatment recommendation for WD is intravenous ceftriaxone, 2 g every 12 h for 2 weeks followed by oral double strength trimethoprim–sulfamethoxazole twice daily for 1–2 years (Feurle and Marth 1994; Marth 2001, 2009). In general WD, the gastrointestinal symptoms respond first, but response of neurologic symptoms, particularly in CNS WD and isolated CNS WD, may require weeks to months for a response, with some patients experiencing relapse and/or death despite treatment (Feurle and Marth 1994; Famularo et al. 2005; Panegyres et al. 2006). "
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    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.
    Full-text · Article · Nov 2012 · Brain and Behavior
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