Nervous System Whipple's Disease Research Articles

Isolated central nervous system Whipple's disease: Two cases

Although it is an orphan disease, isolated central nervous system Whipple's disease is one of the “must be known” conditions in neurology because it belongs to the list of “treatable disorders”. Here, we present two cases which highlight the importance of early diagnosis. Additionally, we provide a discussion on up to date diagnostic approach to this life-threatening disorder.

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.

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

Use of diffusion-weighted imaging in recurrent central nervous system Whipple's disease: a case report and review of the literature

A case of Whipple's disease with development of antibiotic resistance is reported. The patient's symptomatology correlated with evolution of diffusion abnormality rather than with lesion enhancement. The lesion demonstrated no hyperperfusion, moderately elevated choline, and decreased N-acetylaspartate. Conventional magnetic resonance (MR) imaging findings of central nervous system Whipple's disease are nonspecific and may mimic neoplasm. MR perfusion and spectroscopy findings are reported, which may assist in diagnosis. Change in diffusion restriction appears to be a potential imaging indicator of clinical progression and response to therapy.

Whipple’s Disease: Neurological Relapse Presenting as Headache for Two Years

Whipple's disease is a rare, chronic, multi-systemic infectious disorder caused by the bacterium, Tropheryma whipplei. Relapses are commonly associated with neurological symptoms. We report a case of a 55-year-old man who presented with symptoms of progressive headache, 13 years after apparent complete recovery from intestinal Whipple's disease. Studies showed hydrocephalus with obstruction of the aqueduct and cerebrospinal fluid findings consistent with chronic meningitis. Diagnosis of central nervous system Whipple's disease was confirmed by analysis of the cerebrospinal fluid using polymerase chain reaction. After one year of antibiotic therapy, symptoms resolved and cerebrospinal fluid pleocytosis had improved. This case illustrates that Whipple's disease should be included in the differential diagnosis of central nervous system disorders as it is a potentially treatable cause of chronic meningitis. Failure to recognize this presentation can lead to misdiagnosis or a significant delay in diagnosis and treatment.

Isolated central nervous system Whipple's disease causing reversible frontotemporal-like dementia

We report a patient with a syndrome resembling frontotemporal dementia (FTD); however, on further diagnostic testing, the diagnosis was Whipple's disease. Because Whipple's disease is treatable, it should be considered in the workup of patients with a FTD-like behavioural and cognitive syndrome.

Possible Case of CNS Whipple's Disease in an Adolescent With AIDS

An adolescent with HIV/AIDS presented subacutely with progressive encephalopathy, spastic quadraplegia, and diarrhea. His brain biopsy was suggestive of central nervous system Whipple's disease, a disease rarely described in HIV patients. Due to overlapping, nonspecific symptoms associated with several opportunistic infections and to the difficulty in culturing the causative organism Tropheryma whipplei, Whipple's disease may be more common than previously suspected, and it is an important consideration in patients with AIDS.

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.

Oculofacial‐skeletal myorhythmia in central nervous system Whipple's disease: Additional case and review of the literature

A case of oculofacial-skeletal myorhythmia associated with cerebral Whipple's disease is presented. This peculiar abnormal movement disorder consists of a convergent-divergent pendular nystagmus associated with a synchronous, rhythmic movement of the mouth, jaw, and extremities. The movements in previous cases have responded inconsistently to a variety of broad-spectrum antibiotic drugs, and antiepileptic, muscle relaxant, antispastic, and psychotropic drugs. The current patient's mental status improved after starting intravenous ceftriaxone but improvement of the abnormal movements occurred only after the addition of oral valproate. Current treatment consists of intravenous trimethoprim-sulfamethoxazole for 2 weeks followed by oral trimethoprim-sulfamethoxazole twice daily for 1 year. Presented here is an alternative treatment of intravenous ceftriazone followed by oral trimethoprim-sulfamethoxazole in combination with valproate for abnormal movements not responsive to antibiotic drugs alone.

Central nervous system Whipple's disease: Relapse during therapy with trimethoprim-sulfamethoxazole and remission with cefixime

The central nervous system (CNS) is frequently involved in patients with Whipple's disease and is the most common site of disease relapse. Antibiotics such as trimethoprim-sulfamethoxazole (TMP-SMX) that have reliable CNS penetration, are therefore recommended as first-line therapy. We report a patient with Whipple's disease who was treated with TMP-SMX and presented 14 months after initiation of therapy with visual decline and severe headaches. The patient was also treated concurrently with low-dose weekly methotrexate for severe psoriasis. Evaluation by magnetic resonance imaging revealed bilateral posterior white matter abnormalities that pathologically were consistent with Whipple's disease. He was ultimately treated with cefixime, an orally administered third-generation cephalosporin. Visual function improved on this regimen and follow-up magnetic resonance imaging showed regression of the lesions. This case represents the first report of both CNS relapse during therapy with TMP-SMX and successful treatment with cefixime. We also speculate that methotrexate, which impairs cellmediated immunity, may have contributed to the relapse.