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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    • "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.
    The Open Neurology Journal 06/2015; 9(1):21-3. DOI:10.2174/1874205X01509010021
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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.
    Brain and Behavior 11/2012; 2(6):838-43. DOI:10.1002/brb3.97 · 2.24 Impact Factor
    • "The spirochetes, Treponema pallidum and Borrelia burgdorferi, cause neuro-syphilis and Lyme disease, respectively.[22] T. whipplerii, which causes Whipple's disease, can cause chronic neurological manifestations in some patients.[23] However, none of these bacterial pathogens are known to cause CNS demyelination. "
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    ABSTRACT: Interplay between susceptibility genes and environmental factors is considered important player in the genesis of multiple sclerosis (MS). Among environmental factors, a role for an infectious pathogen has long been considered central to the disease process. This opinion has support both from epidemiological data and the findings of immunological abnormalities in spinal fluid that reflect an immune response to an as yet undetermined antigen, possibly a pathogen, in the cerebrospinal fluid. Our review will outline the current understanding of the role of infection in the causation and progression of MS. We will review the data that point to an infectious cause of MS and consider the specific agents Chlamydophila (Chlamydia) pneumoniae, Human Herpes Virus 6, and Epstein-Barr Virus, that are implicated in either the development or progression of MS.
    Annals of Indian Academy of Neurology 04/2010; 13(2):80-6. DOI:10.4103/0972-2327.64622 · 0.60 Impact Factor
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