Central Nervous System Whipple Disease Research Articles

Isolated central nervous system Whipple disease.

Whipple disease (WD) is an infection caused by Tropheryma whipplei, which might present in three different forms: classical, localized, and isolated in the central nervous system (CNS). We report the result of a systematic review of the literature on WD unusually presenting with exclusively neurological symptoms, including two previously unpublished cases. A description of two cases with isolated CNS WD was performed, as well as a literature search in Cochrane, Scielo, and PubMed. Two male adult patients presented with exclusively neurological symptomatology. Both magnetic resonance imaging (MRI) showed an intracranial mass suggestive of brain tumor. The histopathological examination was consistent with WD, with no systemic involvement. In the review of the literature, 35 cases of isolated CNS WD were retrieved. The median age at diagnosis was 43.5 (IQR 31.5-51.5). In 13 patients, the MRI showed a brain mass consistent with a brain tumor. The most common finding in the biopsy was the periodic-acid Schiff-stained foamy macrophages. Only five cases presented the pathognomonic sign of oculomasticatory myorhythmia. Thirteen cases had an adverse outcome that resulted in death during follow-up, whereas another 13 improved. The other nine patients remained stable or presented moderate improvement. Isolated CNS WD is a rare disease that should be considered among the differential diagnosis of CNS mass lesions. Brain biopsy is necessary to establish the diagnosis. It is stressed in the literature that an extended antibiotic course is required to prevent relapses and to control the disease.

Clinical and Neuropathological Variability in Clinically Isolated Central Nervous System Whipple's Disease

Central nervous system Whipple's disease (CNS-WD) with clinically isolated neurological involvement is a rare condition fatal without an early diagnosis. We aimed to present clinical and neuropathological features of three cases of pre- or post-mortem polymerase chain reaction confirmed CNS-WD with distinct clinical presentation, outcome and pathological findings. One patient had an acute onset with spinal and brainstem involvement and died without CNS-WD diagnosis after 14 weeks. Neuropathology showed extensive inflammatory and necrotizing lesions with abundant foamy periodic-acid-Schiff (PAS)+ macrophages. The second patient had a subacute evolution with late CNS-WD diagnosis and death occurring 18 months after onset despite antibiotic treatment. Brain examination showed inflammatory lesions in the brainstem, thalamus and cerebellum, and abundant foamy PAS+ macrophages. The third case was diagnosed within 4 weeks of onset and treated with an excellent response. He died after a disease-free period of 24 months of unrelated causes. Neuropathology showed cystic residual lesions devoid of microorganisms without inflammatory reaction. CNS-WD may have an acute or subacute course with variable response to treatment. Accordingly, subjacent lesions may be those of a severe acute necrotizing encephalitic process or subacute inflammatory lesions involving diencephalic, brainstem, cerebellar and spinal regions. Chronic, cavitary brain lesions may be sequelae of a successful treatment. Early diagnosis should allow appropriate treatment and improve prognosis.

Isolated CNS Whipple disease with normal brain MRI and false‐positive CSF 14‐3‐3 protein: a case report and review of the literature

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.

Atypical central nervous system Whipple's disease: a case report and review of the literature

Objective To report the first case of central nervous system Whipple's disease (WD) with relatively good prognosis in China and present a brief review of central nervous system WD so as to improve the understanding of the diagnosis and treatment of this rare disease. Methods The clinical data of diagnosis, treatment and prognosis of one case of 35-year-old female was analysed in detail. Results Headache, hemiplesia and dementia were the main symptoms of this case and hypercranial pressure crisis occurred. During the course of disease, the patient successively presented paroxysmal extremity convulsion, right leg weakness, urinary incontinence, overeating, body mass increase. Despite of high dose of corticosteroid, penicillin and compound sulfamethoxazole were used, no effect was seen. Along with the increasing of intracranial pressure, cerebral hernia occurred. Cerebrospinal fluid examination indicated that glucose and chloride were normal while protein was obviously increased to 1700 mg/L. Electrocardiography (EEG) showed slow wave in right frontal and temporal lobes. Serial magnetic resonance imaging (MRI) revealed mutiple long T1 and long T2 signals mainly in right cerebral hemisphere, frontal parietal temporal lobes, semioval center and basal ganglion, with edema and irregular loose contrast and extended to left cerebral. Brain biopsy showed large pieces of necrosis at right fronto-temporal lobe with massive infiltration of lymphocytes and plasmocytes at perivascular and brain tissue, and exudation of glitter cells. Positive PAS and methenamine silver staining revealed bacterial particles inglitter cells. Central nervous system tumor, demyelinating disease and inflammatory pseudotumor were excluded. Both clinical symptoms and neuroimging recovered well after regular antibiotic therapy. Conclusion Central nervous system WD is a rare disease with complicated symptoms and imaging characters challenging diagnosis and treatment. The pathological findings may only indicate a special infection of central nervous system with unknown origin. The management is difficult. The misdiagnosis rate and fatality are high. It is important for clinicians to be aware of the features of this disease and make early decision to perform brain biopsy for diagnosis. Once it is diagnosed, normalized therapy should be given. DOI：10.3969/j.issn.1672-6731.2011.05.017

Whipple disease of the central nervous system: an unusual occurrence in association with acquired immune deficiency syndrome

Whipple disease is a multisystem infectious disease caused by Tropheryma whippleii. It commonly affects the CNS and produces neurological symptoms in 10-20% of cases. Central nervous system Whipple disease occurring in patients with AIDS is extremely rare. The authors present a case of a newly diagnosed AIDS patient in whom intracranial Whipple disease was diagnosed by stereotactic brain biopsy.

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

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.

Polymerase chain reaction-based detection of Tropheryma whippelii in central nervous system Whipple's disease.

Whipple's disease of the central nervous system (CNS) may be associated with normal intestinal histology as a result of minimal or patchy involvement. The diagnosis is difficult and is frequently made post mortem. We studied 6 patients with clinically suspected CNS Whipple's disease; 2 had oculomasticatury myorhythmia (OMM) fitting criteria for a diagnosis of definite CNS Whipple's disease. One of the 2 had duodenal histology highly suggestive of Whipple's disease the other 5 patients had normal duodenal histology. DNA was extracted from paraffin-embedded duodenal tissues in all patients and frozen pontine tissue in 1. Two primer pairs (W3F-W4R, W3F-W2R) were used in separate polymerase chain reactions (PCRs) to amplify fragments of Tropberyma whippelii 16S rDNA from these tissue samples. PCR amplicons were detected only in the duodenal tissues from the 2 patients with OMM. The sequences of these amplicons were identical to the corresponding region of the previously published Tropheryma whippelii 16S rDNA sequence. PCR-based assays of intestinal or brain tissue may be of value for confirming, and possibly refuting, a clinical diagnosis of CNS Whipple's disease in a patient with any combination of dementia, supranuclear gaze palsy, hypothalamic manifestations, myoclonus, seizures, ataxia, or OMM, especially when tissue histology is unrevealing.

Whipple's disease and the central nervous system a case report and a review of the literature

A 65-year-old man was suffering from recurrent manic psychosis accompanied by weight loss. He also had a history of pleural effusion, aspecific migratory non-deforming seronegative polyarthritis, sensorineural hearing loss and semicircular canal paresis. Whipple's disease (WD) had been diagnosed at the age of 63 years. On admission to hospital)he had weight loss, diarrhoea in combination with an organic, brain syndrome, hemiparesis and ophthalmoplegia, including internuclear ophthalmoplegia (INO). A clinical diagnosis of central nervous system (CNS) WD was made. MRI revealed a thalamus lesion that halved in size during sulfamethoxazole-trimethop:rim treatment. The organic brain syndrome and ophthalmoplegia diminished also, as did the cerebrospinal fluid (CSF) IgG level. A review of CNS WD is presented and implications for treatment are discussed.

Autoantibodies and rheumatic disorders in a neurology inpatient population: a prospective study

Purpose To determine the prevalence and spectrum of underlying rheumatic diseases, especially Sjögren's syndrome (SS) and the antiphospholipid syndrome, and the prevalence of the lupus anticoagulant, antinuclear antibody (ANA), and rheumatoid factor (RF) within a neurologic patient population. Patients and Methods The study design entailed a prospective, consecutive sample of patients admitted to a university-affiliated neurology service for 72 hours or more. Study patients were obtained from a sequential evaluation of 100 inpatients with a wide spectrum of neurologic diseases. Another 31 eligible patients were not included due to refusal (n = 4), inability to give consent (n = 12), or an incomplete database (n = 15). All patients underwent a physical examination and responded to a rheumatic disease questionnaire (administered by one rheumatologist) assessing signs and symptoms relevant to rheumatic disease. All had lupus anticoagulant, ANA, and RF determinations. An independent patient evaluation was done by the attending neurologist. Results Eleven patients had a rheumatic or autoimmune disorder directly related to their neurologic admission: three patients with SS (one each with embolic stroke, dementia, and hemiparetic somatization); three patients with lupus anticoagulant syndrome (all with stroke, recurrent in two); one patient with systemic lupus erythematosus accompanied by migraine headache and the lupus anticoagulant; and one patient each with isolated central nervous system (CNS) angiitis, neuro-Behçet's disease, CNS Whipple's disease, and HLA-B27-associated spondyloarthropathy. Nineteen patients had one or more autoantibodies: ANA greater than or equal to 1:80 (n = 10); RF greater than or equal to 1:80 (n = 6); and positive lupus anticoagulant (n = 7). The seroreactivity of 10 of these patients remained unexplained. Conclusions This neurologic population demonstrated significant seroreactivity and rheumatic disease associations, with SS and lupus anticoagulant-related neurologic disease the most common. Since SS and the antiphospholipid syndrome can be overlooked, it is recommended that a formal evaluation for SS and a direct lupus anticoagulant assay should be considered in the examination of patients with neuropsychiatric symptoms. To determine the prevalence and spectrum of underlying rheumatic diseases, especially Sjögren's syndrome (SS) and the antiphospholipid syndrome, and the prevalence of the lupus anticoagulant, antinuclear antibody (ANA), and rheumatoid factor (RF) within a neurologic patient population. The study design entailed a prospective, consecutive sample of patients admitted to a university-affiliated neurology service for 72 hours or more. Study patients were obtained from a sequential evaluation of 100 inpatients with a wide spectrum of neurologic diseases. Another 31 eligible patients were not included due to refusal (n = 4), inability to give consent (n = 12), or an incomplete database (n = 15). All patients underwent a physical examination and responded to a rheumatic disease questionnaire (administered by one rheumatologist) assessing signs and symptoms relevant to rheumatic disease. All had lupus anticoagulant, ANA, and RF determinations. An independent patient evaluation was done by the attending neurologist. Eleven patients had a rheumatic or autoimmune disorder directly related to their neurologic admission: three patients with SS (one each with embolic stroke, dementia, and hemiparetic somatization); three patients with lupus anticoagulant syndrome (all with stroke, recurrent in two); one patient with systemic lupus erythematosus accompanied by migraine headache and the lupus anticoagulant; and one patient each with isolated central nervous system (CNS) angiitis, neuro-Behçet's disease, CNS Whipple's disease, and HLA-B27-associated spondyloarthropathy. Nineteen patients had one or more autoantibodies: ANA greater than or equal to 1:80 (n = 10); RF greater than or equal to 1:80 (n = 6); and positive lupus anticoagulant (n = 7). The seroreactivity of 10 of these patients remained unexplained. This neurologic population demonstrated significant seroreactivity and rheumatic disease associations, with SS and lupus anticoagulant-related neurologic disease the most common. Since SS and the antiphospholipid syndrome can be overlooked, it is recommended that a formal evaluation for SS and a direct lupus anticoagulant assay should be considered in the examination of patients with neuropsychiatric symptoms.

Autoantibodies and rheumatic disorders in a neurology inpatient population: A prospective study

purpose: To determine the prevalence and spectrum of underlying rheumatic diseases, especially Sjögren's syndrome (SS) and the antiphospholipid syndrome, and the prevalence of the lupus anticoagulant, antinuclear antibody (ANA), and rheumatoid factor (RF) within a neurologic patient population. patients and methods: The study design entailed a prospective, consecutive sample of patients admitted to a university-affiliated neurology service for 72 hours or more. Study patients were obtained from a sequential evaluation of 100 inpatients with a wide spectrum of neurologic diseases. Another 31 eligible patients were not included due to refusal ( n = 4), inability to give consent (n = 12), or an incomplete database ( n = 15). All patients underwent a physical examination and responded to a rheumatic disease questionnaire (administered by one rheumatologist) assessing signs and symptoms relevant to rheumatic disease. All had lupus anticoagulant, ANA, and RF determinations. An independent patient evaluation was done by the attending neurologist. results: Eleven patients had a rheumatic or autoimmune disorder directly related to their neurologic admission: three patients with SS (one each with embolic stroke, dementia, and hemiparetic somatization); three patients with lupus anticoagulant syndrome (all with stroke, recurrent in two); one patient with systemic lupus erythematosus accompanied by migraine headache and the lupus anticoagulant; and one patient each with isolated central nervous system (CNS) angiitis, neuro-Behçet's disease, CNS Whipple's disease, and HLA-B27-associated spondyloarthropathy. Nineteen patients had one or more autoantibodies: ANA greater than or equal to 1:80 ( n = 10); RF greater than or equal to 1:80 ( n = 6); and positive lupus anticoagulant (n = 7). The seroreactivity of 10 of these patients remained unexplained. conclusions: This neurologic population demonstrated significant seroreactivity and rheumatic disease associations, with SS and lupus anticoagulant-related neurologic disease the most common. Since SS and the antiphospholipid syndrome can be overlooked, it is recommended that a formal evaluation for SS and a direct lupus anticoagulant assay should be considered in the examination of patients with neuropsychiatric symptoms.