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Mansour MA, Malaeb RW, Elnemr IE, El-Salamoni MAF, Mostafa HN, Ahmadi Z. Central nervous system involvement in Whipple's disease: Report of a rare pathological entity and comparative review of treatment strategies and outcomes. Radiol Case Rep 2025; 20:1425-1430. [PMID: 39807114 PMCID: PMC11728665 DOI: 10.1016/j.radcr.2024.11.045] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Revised: 11/06/2024] [Accepted: 11/17/2024] [Indexed: 01/16/2025] Open
Abstract
Whipple's disease, caused by the gram-positive actinomycete Tropheryma whipplei, is a rare chronic systemic illness with significant diagnostic and therapeutic challenges, particularly when the CNS is involved. This case report details a 46-year-old man presenting with a constellation of symptoms including fatigue, hypersomnia, weight loss, bifrontal headaches, abdominal pain, treatment-unresponsive diarrhea, and skin hyperpigmentation. Neurological examination revealed oculomasticatory myorhythmia, and imaging studies showed nodular enhancement of the hypothalamus and basal ganglia, along with retroperitoneal lymphadenopathy. Diagnosis was confirmed through duodenal biopsy with PAS staining and PCR analysis. The patient was successfully treated with a combination of intravenous ceftriaxone followed by oral doxycycline and hydroxychloroquine, resulting in significant symptom improvement and full recovery of neurological function. This case underscores the importance of early, aggressive treatment and provides a comprehensive review of the current literature on Whipple's disease with CNS involvement, including a comparison of treatment regimens and outcomes.
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Affiliation(s)
- Moustafa A. Mansour
- Department of Neurosurgery, Nasser Institute for Research and Treatment, Cairo, Egypt
- Department of Neurology and Neurosurgery, Faculty of Medicine, Al-Azhar University, Cairo, Egypt
| | - Reem W. Malaeb
- Department of Health Professions, Faculty of Health Sciences, American University of Beirut, Beirut, Lebanon
| | - Islam E. Elnemr
- Department of Neurosurgery, Nasser Institute for Research and Treatment, Cairo, Egypt
| | | | - Hamdi Nabawi Mostafa
- Department of Neurosurgery, Nasser Institute for Research and Treatment, Cairo, Egypt
- Department of Neurosurgery, Misr University for Science and Technology, Giza, Egypt
| | - Zarina Ahmadi
- Department of Infectious Diseases and Tropical Medicine, Faculty of Medicine, Al-Azhar University, Cairo, Egypt
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Desai AB, Agarwal A, Mohamed AS, Mohamed KH, Middlebrooks EH, Bhatt AA, Gupta V, Kumar N, Sechi E, Flanagan EP, López Chiriboga S. Motor Neuron Diseases and Central Nervous System Tractopathies: Clinical-Radiologic Correlation and Diagnostic Approach. Radiographics 2025; 45:e240067. [PMID: 39636751 DOI: 10.1148/rg.240067] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/07/2024]
Abstract
White matter tracts within the central nervous system are organized into ascending and descending pathways that transmit sensory input and motor output, respectively. Tractopathy, or damage to these tracts, can impair sensory or motor functions. Motor neuron diseases are pathologic processes affecting the upper or lower motor neurons. Amyotrophic lateral sclerosis (ALS) is the most common form of acquired motor neuron disease. Traditionally, ALS has affected upper and lower motor neurons of the extremities, torso, and head and neck. There are several ALS variants, some of which affect only the upper motor neurons (eg, primary lateral sclerosis), lower motor neurons (eg, progressive muscular atrophy), or motor neurons of the head and neck (eg, progressive bulbar palsy). Characteristic imaging features of ALS include abnormal T2 hyperintensity within the brain along the corticospinal tract, as well as cortical susceptibility signal intensity along the precentral gyrus, termed the "motor band" sign. Spinal muscular atrophy is a less common primary motor neuron disease and appears on images as atrophy of the anterior horn of the spinal cord, as well as proximal muscle atrophy. In addition to pure motor neuron diseases, there are numerous toxic and metabolic conditions, genetic disorders, infectious diseases, and immune-mediated disorders that can secondarily affect the corticospinal tracts (corticospinal tractopathies), producing symptoms of upper motor neuron injury. These tractopathies are visible at MRI as T2-hyperintense lesions along varying segments of the corticospinal tract. A comprehensive diagnostic approach that integrates clinical symptoms with radiologic and laboratory findings is crucial to distinguish among these varied conditions. ©RSNA, 2024 Supplemental material is available for this article.
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Affiliation(s)
- Amit B Desai
- From the Departments of Radiology (A.B.D., A.A., E.H.M., A.A.B., V.G.) and Neurology (A.S.M., K.H.M., S.L.C.), Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224; Department of Neurology, Mayo Clinic, Rochester, MN (N.K., E.S., E.P.F.); and Department of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari, Italy (E.S.)
| | - Amit Agarwal
- From the Departments of Radiology (A.B.D., A.A., E.H.M., A.A.B., V.G.) and Neurology (A.S.M., K.H.M., S.L.C.), Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224; Department of Neurology, Mayo Clinic, Rochester, MN (N.K., E.S., E.P.F.); and Department of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari, Italy (E.S.)
| | - Alaa S Mohamed
- From the Departments of Radiology (A.B.D., A.A., E.H.M., A.A.B., V.G.) and Neurology (A.S.M., K.H.M., S.L.C.), Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224; Department of Neurology, Mayo Clinic, Rochester, MN (N.K., E.S., E.P.F.); and Department of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari, Italy (E.S.)
| | - Khalid H Mohamed
- From the Departments of Radiology (A.B.D., A.A., E.H.M., A.A.B., V.G.) and Neurology (A.S.M., K.H.M., S.L.C.), Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224; Department of Neurology, Mayo Clinic, Rochester, MN (N.K., E.S., E.P.F.); and Department of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari, Italy (E.S.)
| | - Erik H Middlebrooks
- From the Departments of Radiology (A.B.D., A.A., E.H.M., A.A.B., V.G.) and Neurology (A.S.M., K.H.M., S.L.C.), Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224; Department of Neurology, Mayo Clinic, Rochester, MN (N.K., E.S., E.P.F.); and Department of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari, Italy (E.S.)
| | - Alok A Bhatt
- From the Departments of Radiology (A.B.D., A.A., E.H.M., A.A.B., V.G.) and Neurology (A.S.M., K.H.M., S.L.C.), Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224; Department of Neurology, Mayo Clinic, Rochester, MN (N.K., E.S., E.P.F.); and Department of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari, Italy (E.S.)
| | - Vivek Gupta
- From the Departments of Radiology (A.B.D., A.A., E.H.M., A.A.B., V.G.) and Neurology (A.S.M., K.H.M., S.L.C.), Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224; Department of Neurology, Mayo Clinic, Rochester, MN (N.K., E.S., E.P.F.); and Department of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari, Italy (E.S.)
| | - Neeraj Kumar
- From the Departments of Radiology (A.B.D., A.A., E.H.M., A.A.B., V.G.) and Neurology (A.S.M., K.H.M., S.L.C.), Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224; Department of Neurology, Mayo Clinic, Rochester, MN (N.K., E.S., E.P.F.); and Department of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari, Italy (E.S.)
| | - Elia Sechi
- From the Departments of Radiology (A.B.D., A.A., E.H.M., A.A.B., V.G.) and Neurology (A.S.M., K.H.M., S.L.C.), Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224; Department of Neurology, Mayo Clinic, Rochester, MN (N.K., E.S., E.P.F.); and Department of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari, Italy (E.S.)
| | - Eoin P Flanagan
- From the Departments of Radiology (A.B.D., A.A., E.H.M., A.A.B., V.G.) and Neurology (A.S.M., K.H.M., S.L.C.), Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224; Department of Neurology, Mayo Clinic, Rochester, MN (N.K., E.S., E.P.F.); and Department of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari, Italy (E.S.)
| | - Sebastian López Chiriboga
- From the Departments of Radiology (A.B.D., A.A., E.H.M., A.A.B., V.G.) and Neurology (A.S.M., K.H.M., S.L.C.), Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224; Department of Neurology, Mayo Clinic, Rochester, MN (N.K., E.S., E.P.F.); and Department of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari, Italy (E.S.)
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Almeida FC, Pereira AI, Mendes-Pinto C, Lopes J, Moura J, Sousa JM, Videira G, Samões R, Oliveira TG. MR Imaging Findings in Anti-Leucine-Rich Glioma Inactivated Protein 1 Encephalitis: A Systematic Review and Meta-analysis. AJNR Am J Neuroradiol 2024; 45:977-986. [PMID: 38871367 DOI: 10.3174/ajnr.a8256] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2023] [Accepted: 02/14/2024] [Indexed: 06/15/2024]
Abstract
BACKGROUND Antibodies against leucine-rich glioma inactivated protein 1 (LGI1) constitute a common form of autoimmune encephalitis. On MR imaging, it may show T2 FLAIR hyperintensities of the medial temporal lobe (T2 FLAIR-MTL), involve the basal ganglia, or be unremarkable. PURPOSE We performed a systematic review and meta-analysis to obtain prevalence estimates of abnormal findings on MR imaging in anti-LGI1 encephalitis. A human brain map of the LGI1 microarray gene expression was derived from the Allen Human Brain Atlas. DATA SOURCES PubMed and Web of Science were searched with the terms "LGI1" and "encephalitis" from inception to April 7, 2022. STUDY SELECTION Thirty-one research publications, encompassing case series and retrospective cohort and case-control studies, with >10 patients with anti-LGI1 encephalitis and MR imaging data were included. DATA ANALYSIS Pooled prevalence estimates were calculated using Freeman-Tukey double-arcsine transformation. Meta-analysis used DerSimonian and Laird random effects models. DATA SYNTHESIS Of 1318 patients in 30 studies, T2 FLAIR-MTL hyperintensities were present in 54% (95% CI, 0.48-0.60; I2 = 76%). Of 394 patients in 13 studies, 27% showed bilateral (95% CI, 0.19-0.36; I2 = 71%) and 24% unilateral T2 FLAIR-MTL abnormalities (95% CI, 0.17-0.32; I2 = 61%). Of 612 patients in 15 studies, basal ganglia abnormalities were present in 10% (95% CI, 0.06-0.15; I2 = 67%). LGI1 expression was highest in the amygdala, hippocampus, and caudate nucleus. LIMITATIONS Only part of the spectrum of MR imaging abnormalities in anti-LGI1 encephalitis could be included in a meta-analysis. MR imaging findings were not the main outcomes in most studies, limiting available information. I2 values ranged from 62% to 76%, representing moderate-to-large heterogeneity. CONCLUSIONS T2 FLAIR-MTL hyperintensities were present in around one-half of patients with anti-LGI1. The prevalence of unilateral and bilateral presentations was similar, suggesting unilaterality should raise the suspicion of this disease in the appropriate clinical context. Around 10% of patients showed basal ganglia abnormalities, indicating that special attention should be given to this region. LGI1 regional expression coincided with the most frequently reported abnormal findings on MR imaging. Regional specificity might be partially determined by expression levels of the target protein.
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Affiliation(s)
- Francisco C Almeida
- From the Department of Neuroradiology (F.C.A., A.I.P., C.M.-P.), Centro Hospitalar Universitário de Santo António, Porto, Portugal
- Life and Health Sciences Research Institute (F.C.A., T.G.O.), School of Medicine, University of Minho, Braga, Portugal
- Life and Health Sciences Research Institute/3B's-PT Government Associate Laboratory (F.C.A., T.G.O.), Braga/Guimarães, Portugal
| | - Ana I Pereira
- From the Department of Neuroradiology (F.C.A., A.I.P., C.M.-P.), Centro Hospitalar Universitário de Santo António, Porto, Portugal
| | - Catarina Mendes-Pinto
- From the Department of Neuroradiology (F.C.A., A.I.P., C.M.-P.), Centro Hospitalar Universitário de Santo António, Porto, Portugal
| | - Joana Lopes
- Department of Neurology (J.L., J.M., G.V., R.S.), Centro Hospitalar Universitário de Santo António, Porto, Portugal
| | - João Moura
- Department of Neurology (J.L., J.M., G.V., R.S.), Centro Hospitalar Universitário de Santo António, Porto, Portugal
| | - José Maria Sousa
- Department of Neuroradiology (J.M.S.), Centro Hospitalar Universitário de São João, Porto, Portugal
| | - Gonçalo Videira
- Department of Neurology (J.L., J.M., G.V., R.S.), Centro Hospitalar Universitário de Santo António, Porto, Portugal
| | - Raquel Samões
- Department of Neurology (J.L., J.M., G.V., R.S.), Centro Hospitalar Universitário de Santo António, Porto, Portugal
- Unit for Multidisciplinary Research in Biomedicine (R.S.), Instituto de Ciências Biomédicas de Abel Salazar da Universidade do Porto, Porto, Portugal
| | - Tiago Gil Oliveira
- Life and Health Sciences Research Institute (F.C.A., T.G.O.), School of Medicine, University of Minho, Braga, Portugal
- Life and Health Sciences Research Institute/3B's-PT Government Associate Laboratory (F.C.A., T.G.O.), Braga/Guimarães, Portugal
- Department of Neuroradiology (T.G.O.), Hospital de Braga, Braga, Portugal
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Biddle G, Beck RT, Raslan O, Ebinu J, Jenner Z, Hamer J, Hacein-Bey L, Apperson M, Ivanovic V. Autoimmune diseases of the spine and spinal cord. Neuroradiol J 2024; 37:285-303. [PMID: 37394950 PMCID: PMC11138326 DOI: 10.1177/19714009231187340] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/04/2023] Open
Abstract
Magnetic resonance imaging (MRI) and clinicopathological tools have led to the identification of a wide spectrum of autoimmune entities that involve the spine. A clearer understanding of the unique imaging features of these disorders, along with their clinical presentations, will prove invaluable to clinicians and potentially limit the need for more invasive procedures such as tissue biopsies. Here, we review various autoimmune diseases affecting the spine and highlight salient imaging features that distinguish them radiologically from other disease entities.
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Affiliation(s)
- Garrick Biddle
- Radiology Department, University of California Davis School of Medicine, Sacramento, CA, USA
| | - Ryan T Beck
- Neuroradiology, Radiology Department, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Osama Raslan
- Radiology Department, University of California Davis School of Medicine, Sacramento, CA, USA
| | - Julius Ebinu
- Neurosurgery Department, University of California Davis School of Medicine, Sacramento, CA, USA
| | - Zach Jenner
- Radiology Department, University of California Davis School of Medicine, Sacramento, CA, USA
| | - John Hamer
- Neuroradiology, Radiology Department, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Lotfi Hacein-Bey
- Radiology Department, University of California Davis School of Medicine, Sacramento, CA, USA
| | - Michelle Apperson
- Neurology Department, University of California Davis School of Medicine, Sacramento, CA, USA
| | - Vladimir Ivanovic
- Neuroradiology, Radiology Department, Medical College of Wisconsin, Milwaukee, WI, USA
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Jakabek D, Chaganti J, Brew BJ. Infectious leukoencephalopathies. HANDBOOK OF CLINICAL NEUROLOGY 2024; 204:431-453. [PMID: 39322393 DOI: 10.1016/b978-0-323-99209-1.00016-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/27/2024]
Abstract
Leukoencephalopathy from infectious agents may have a rapid course, such as human simplex virus encephalitis; however, in many diseases, it may take months or years before diagnosis, such as in subacute sclerosing panencephalitis or Whipple disease. There are wide geographic distributions and susceptible populations, including both immunocompetent and immunodeficient patients. Many infections have high mortality rates, such as John Cunningham virus and subacute sclerosing panencephalitis, although others have effective treatments if suspected and treated early, such as herpes simplex encephalitis. This chapter will describe viral, bacterial, and protozoal infections, which predominantly cause leukoencephalopathy. We focus on the clinical presentation of these infectious agents briefly covering epidemiology and subtypes of infections. Next, we detail current pathophysiologic mechanisms causing white matter injury. Diagnostic and confirmatory tests are discussed. We cover predominantly MRI imaging features of leukoencephalopathies, and in addition, summarize the common imaging features. Additionally, we detail how imaging features may be used to narrow the differential of a leukoencephalopathy clinical presentation. Lastly, we present an outline of common treatment approaches where available.
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Affiliation(s)
- David Jakabek
- Department of Neurology, St. Vincent's Hospital, Sydney, NSW, Australia; University of New South Wales, Sydney, NSW, Australia
| | - Joga Chaganti
- Department of Radiology, St. Vincent's Hospital, Sydney, NSW, Australia
| | - Bruce James Brew
- Department of Neurology, St. Vincent's Hospital, Sydney, NSW, Australia; University of New South Wales, Sydney, NSW, Australia; University of Notre Dame, Sydney, NSW, Australia; Department of HIV Medicine and Peter Duncan Neurosciences Unit St Vincent's Centre for Applied Medical Research, St. Vincent's Hospital, Sydney, NSW, Australia.
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Mecklenburg J, Moos V, Moter A, Siebert E, Nave AH, Schneider T, Ruprecht K, Euskirchen P. The spectrum of central nervous system involvement in Whipple's disease. Eur J Neurol 2023; 30:3417-3429. [PMID: 35852414 DOI: 10.1111/ene.15511] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2022] [Accepted: 06/29/2022] [Indexed: 11/27/2022]
Abstract
BACKGROUND AND PURPOSE To assess the clinical spectrum of central nervous system (CNS) involvement as well as cerebrospinal fluid (CSF) and neuroimaging findings in patients with Whipple's disease (WD) and to analyze the association of neurological symptoms with CSF and imaging findings. METHODS Neurological involvement was retrospectively analyzed in a series of 36 patients diagnosed with WD at a single center between 1992 and 2019. Findings of 81 comprehensive CSF examinations from 36 patients, including polymerase chain reaction (PCR) tests for Tropheryma whipplei (TW) in CSF from 35 patients, were systematically evaluated. The prevalence of ischemic stroke in patients with WD was compared to a matched control cohort. RESULTS Neurological symptoms occurred in 23 of 36 (63.9%) patients, with cognitive, motor, and oculomotor dysfunction being most frequent. TW was detected by PCR in CSF of 13 of 22 (59.1%) patients with and four of 13 (30.8%, p = 0.0496) patients without neurological symptoms. Total CSF protein (p = 0.044) and lactate (p = 0.035) were moderately elevated in WD with neurologic symptoms compared with WD without. No intrathecal immunoglobulin synthesis was observed. Three of 36 (8.3%) patients had hydrocephalus due to aqueductal stenosis. Patients with WD had an unexpectedly high prevalence of ischemic stroke (10/36, 27.7%) compared to matched controls (10/360, 3.2%). CONCLUSIONS Neurological involvement in patients with WD is common. Detection of TW DNA in CSF is only partly associated with neurological symptoms. Elevated CSF parameters suggest CNS parenchymal infection. Stroke is a hitherto underrecognized manifestation of WD. These findings suggest that mechanisms beyond CNS infection contribute to the spectrum of CNS involvement in WD.
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Affiliation(s)
- Jasper Mecklenburg
- Department of Neurology, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Verena Moos
- Medical Department of Gastroenterology, Rheumatology and Infectious Diseases, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Annette Moter
- Institute for Microbiology, Infectious Diseases and Immunology, Biofilmcenter, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charité - Universitätsmedizin Berlin, Berlin, Germany
- MoKi Analytics and Moter Diagnostics, Berlin, Germany
| | - Eberhard Siebert
- Department of Neuroradiology, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Alexander Heinrich Nave
- Department of Neurology, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charité - Universitätsmedizin Berlin, Berlin, Germany
- Center for Stroke Research Berlin (CSB), Berlin, Germany
- Deutsches Zentrum für Herz-Kreislauferkrankungen (DZHK), Partner Site Berlin, Berlin, Germany
| | - Thomas Schneider
- Medical Department of Gastroenterology, Rheumatology and Infectious Diseases, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Klemens Ruprecht
- Department of Neurology, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Philipp Euskirchen
- Department of Neurology, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charité - Universitätsmedizin Berlin, Berlin, Germany
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Imaging of Uncommon Bacterial, Rickettsia, Spirochete, and Fungal Infections. Neuroimaging Clin N Am 2023; 33:83-103. [DOI: 10.1016/j.nic.2022.07.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
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Barbero-Aznarez P, Perez-Tanoira R, Aguirre-Mollehuanca D, Trascasa-Caño A, Fortes-Alen J, Manzarbeitia-Arrambari F, Castillo-Alvarez J, Montoya-Bordon J, Petkova-Saiz E, Prieto-Perez L. Isolated central nervous system Whipple disease. Surg Neurol Int 2022; 13:477. [DOI: 10.25259/sni_591_2022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Accepted: 09/19/2022] [Indexed: 11/04/2022] Open
Abstract
Background:
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).
Methods:
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.
Results:
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.
Conclusion:
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.
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Affiliation(s)
- Pablo Barbero-Aznarez
- Department of Neurosurgery, Instituto Clavel, San Francisco De Asis University Hospital, Madrid, Spain
| | - Ramon Perez-Tanoira
- Department of Microbiology, Principe de Asturias University Hospital, Madrid, Spain
| | | | | | - Jose Fortes-Alen
- Department of Pathology, Fundacion Jimenez Diaz University Hospital, Madrid, Spain
| | | | | | | | | | - Laura Prieto-Perez
- Internal Medicine, Fundacion Jimenez Diaz University Hospital, Madrid, Spain
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de Oliveira Santana MA, Butt S, Nassiri M. Central Nervous System Whipple Disease Presenting as Hypersomnolence. Cureus 2022; 14:e23572. [PMID: 35494928 PMCID: PMC9045463 DOI: 10.7759/cureus.23572] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/28/2022] [Indexed: 01/18/2023] Open
Abstract
Whipple disease (WD) is a rare systemic infection caused by Tropheryma whipplei (T. whipplei). Its clinical features are broad, and atypical clinical patterns such as the involvement of the heart, lungs, or the central nervous system (CNS) can occur. We report a case of a 58-year-old man who had been previously diagnosed with classic WD; he was evaluated for functional decline, extreme somnolence, and recurrent admissions for hydrocephalus. The patient was diagnosed with a neurologic relapse of WD after a positive T. whipplei polymerase chain reaction (PCR) from a cerebral spinal fluid (CSF) sample. He was successfully treated with IV ceftriaxone followed by oral trimethoprim-sulfamethoxazole (TMP-SMX). In classic WD, the CNS symptoms usually present in the late phase of the disease or in the form of relapse, especially after an inadequate treatment course. This case highlights the importance of considering CNS involvement in WD when a patient with a previous history of classic WD presents with hypersomnolence, hydrocephalus, or other neurologic symptoms.
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10
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Rapidly progressive dementia and intractable diarrhea: a teaching case report and a systematic review of cognitive impairment in Whipple’s disease. Neurol Sci 2022; 43:907-926. [PMID: 34981284 PMCID: PMC8722651 DOI: 10.1007/s10072-021-05844-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Accepted: 12/22/2021] [Indexed: 11/02/2022]
Abstract
Objective Methods Results Conclusions Supplementary Information
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11
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Ganguly J, Jog M. Tauopathy and Movement Disorders-Unveiling the Chameleons and Mimics. Front Neurol 2020; 11:599384. [PMID: 33250855 PMCID: PMC7674803 DOI: 10.3389/fneur.2020.599384] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2020] [Accepted: 09/30/2020] [Indexed: 12/11/2022] Open
Abstract
The spectrum of tauopathy encompasses heterogenous group of neurodegenerative disorders characterized by neural or glial deposition of pathological protein tau. Clinically they can present as cognitive syndromes, movement disorders, motor neuron disease, or mixed. The heterogeneity in clinical presentation, genetic background, and underlying pathology make it difficult to classify and clinically approach tauopathy. In the literature, tauopathies are thus mostly highlighted from pathological perspective. From clinical standpoint, cognitive syndromes are often been focussed while reviewing tauopathies. However, the spectrum of tauopathy has also evolved significantly in the domain of movement disorders and has transgressed beyond the domain of primary tauopathies. Secondary tauopathies from neuroinflammation or autoimmune insults and some other "novel" tauopathies are increasingly being reported in the current literature, while some of them are geographically isolated. Because of the overlapping clinical phenotypes, it often becomes difficult for the clinician to diagnose them clinically and have to wait for the pathological confirmation by autopsy. However, each of these tauopathies has some clinical and radiological signatures those can help in clinical diagnosis and targeted genetic testing. In this review, we have exposed the heterogeneity of tauopathy from a movement disorder perspective and have provided a clinical approach to diagnose them ante mortem before confirmatory autopsy. Additionally, phenotypic variability of these disorders (chameleons) and the look-alikes (mimics) have been discussed with potential clinical pointers for each of them. The review provides a framework within which new and as yet undiscovered entities can be classified in the future.
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Affiliation(s)
| | - Mandar Jog
- Movement Disorder Centre, London Health Sciences Centre, University of Western Ontario, London, ON, Canada
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12
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Taschner CA, Doostkam S, Reinacher PC, Urbach H, Rau A, Prinz M. Freiburg Neuropathology Case Conference. Clin Neuroradiol 2019; 29:797-804. [DOI: 10.1007/s00062-019-00849-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
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13
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Brönnimann D, Vareil MO, Sibon I, Lagier JC, Lepidi H, Puges M, Haneche F, Raoult D, Desclaux A, Neau D, Cazanave C. Limbic encephalitis as a relapse of Whipple's disease with digestive involvement and spondylodiscitis. Infection 2018; 47:637-641. [PMID: 29987509 DOI: 10.1007/s15010-018-1173-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2017] [Accepted: 07/04/2018] [Indexed: 12/17/2022]
Abstract
INTRODUCTION Many clinical manifestations can be related to Tropheryma whipplei infection. CASE REPORT We report a Tropheryma whipplei limbic encephalitis developed as a relapse of classical Whipple's disease. DISCUSSION This case is to the best of our knowledge the first proof of the effective brain-blood barrier crossing of both doxycycline and hydroxychloroquine as demonstrated by direct concentration monitoring on brain biopsy.
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Affiliation(s)
- Didier Brönnimann
- Service de médecine interne et pathologies infectieuses, CHU de Bordeaux, Groupe Hospitalier Saint André, hôpital Saint André, 1 rue Jean Burguet, 33000, Bordeaux Cedex, France.
| | - Marc-Olivier Vareil
- Service de maladies infectieuses et dermatologie, Centre hospitalier de la côte basque, 64100, Bayonne, France
| | - Igor Sibon
- CHU Bordeaux, Unité Neurovasculaire, 33000, Bordeaux, France.,Univ. Bordeaux, INCIA UMR CNRS 5287, 33000, Bordeaux, France
| | - Jean-Christophe Lagier
- Aix Marseille Université, URMITE, UM 63, CNRS 7278, IRD 198, INSERM 1095, 13000, Marseille, France
| | - Hubert Lepidi
- Aix Marseille Université, URMITE, UM 63, CNRS 7278, IRD 198, INSERM 1095, 13000, Marseille, France
| | - Mathilde Puges
- Service des pathologies infectieuses et tropicales, CHU de Bordeaux, hôpital Pellegrin, 33000, Bordeaux, France
| | - Fatiha Haneche
- Service des pathologies infectieuses et tropicales, CHU de Bordeaux, hôpital Pellegrin, 33000, Bordeaux, France
| | - Didier Raoult
- Aix Marseille Université, URMITE, UM 63, CNRS 7278, IRD 198, INSERM 1095, 13000, Marseille, France
| | - Arnaud Desclaux
- Service des pathologies infectieuses et tropicales, CHU de Bordeaux, hôpital Pellegrin, 33000, Bordeaux, France
| | - Didier Neau
- Service des pathologies infectieuses et tropicales, CHU de Bordeaux, hôpital Pellegrin, 33000, Bordeaux, France
| | - Charles Cazanave
- Service des pathologies infectieuses et tropicales, CHU de Bordeaux, hôpital Pellegrin, 33000, Bordeaux, France.,Univ. Bordeaux, USC EA 3671, Infections humaines à mycoplasmes et à chlamydiae, 33000, Bordeaux, France
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14
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Clinical Manifestations, Treatment, and Diagnosis of Tropheryma whipplei Infections. Clin Microbiol Rev 2017; 30:529-555. [PMID: 28298472 DOI: 10.1128/cmr.00033-16] [Citation(s) in RCA: 97] [Impact Index Per Article: 12.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Whipple's disease is a rare infectious disease that can be fatal if left untreated. The disease is caused by infection with Tropheryma whipplei, a bacterium that may be more common than was initially assumed. Most patients present with nonspecific symptoms, and as routine cultivation of the bacterium is not feasible, it is difficult to diagnose this infection. On the other hand, due to the generic symptoms, infection with this bacterium is actually quite often in the differential diagnosis. The gold standard for diagnosis used to be periodic acid-Schiff (PAS) staining of duodenal biopsy specimens, but PAS staining has a poor specificity and sensitivity. The development of molecular techniques has resulted in more convenient methods for detecting T. whipplei infections, and this has greatly improved the diagnosis of this often missed infection. In addition, the molecular detection of T. whipplei has resulted in an increase in knowledge about its pathogenicity, and this review gives an overview of the new insights in epidemiology, pathogenesis, clinical manifestations, diagnosis, and treatment of Tropheryma whipplei infections.
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15
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Whipple's disease. J Neurol Sci 2017; 377:197-206. [DOI: 10.1016/j.jns.2017.01.048] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2015] [Revised: 12/16/2016] [Accepted: 01/15/2017] [Indexed: 11/24/2022]
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16
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Giaccone G, Carella F, Parravicini C, Longhi E, Chiapparini L, Savoiardo M, Montano N, Morbin M, Albanese A, Tagliavini F. A 52-Year-Old Man with Myoclonic Jerks. Brain Pathol 2016; 26:291-2. [PMID: 27000489 DOI: 10.1111/bpa.12359] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Affiliation(s)
- Giorgio Giaccone
- IRCCS Foundation Carlo Besta Neurological Institute, Milan, Italy
| | | | | | | | | | - Mario Savoiardo
- IRCCS Foundation Carlo Besta Neurological Institute, Milan, Italy
| | - Nicola Montano
- Luigi Sacco Hospital, Milano, Italy.,Department of Biomedical and Clinical Sciences, University of Milano, Milano, Italy
| | - Michela Morbin
- IRCCS Foundation Carlo Besta Neurological Institute, Milan, Italy
| | - Alberto Albanese
- IRCCS Foundation Carlo Besta Neurological Institute, Milan, Italy
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17
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Hale A, Geerling J, Schmolze D, Pfannl R, Karchmer AW. A 63-Year-Old Man With Rapidly Progressive Dementia. Clin Infect Dis 2016; 63:138-9. [DOI: 10.1093/cid/ciw266] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
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Morales H, Tomsick T. Middle cerebellar peduncles: Magnetic resonance imaging and pathophysiologic correlate. World J Radiol 2015; 7:438-447. [PMID: 26751508 PMCID: PMC4697118 DOI: 10.4329/wjr.v7.i12.438] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2015] [Revised: 09/05/2015] [Accepted: 10/27/2015] [Indexed: 02/06/2023] Open
Abstract
We describe common and less common diseases that can cause magnetic resonance signal abnormalities of middle cerebellar peduncles (MCP), offering a systematic approach correlating imaging findings with clinical clues and pathologic mechanisms. Myelin abnormalities, different types of edema or neurodegenerative processes, can cause areas of abnormal T2 signal, variable enhancement, and patterns of diffusivity of MCP. Pathologies such as demyelinating disorders or certain neurodegenerative entities (e.g., multiple system atrophy or fragile X-associated tremor-ataxia syndrome) appear to have predilection for MCP. Careful evaluation of concomitant imaging findings in the brain or brainstem; and focused correlation with key clinical findings such as immunosuppression for progressive multifocal leukoencephalopahty; hypertension, post-transplant status or high dose chemotherapy for posterior reversible encephalopathy; electrolyte disorders for myelinolysis or suspected toxic-drug related encephalopathy; would yield an appropriate and accurate differential diagnosis in the majority of cases.
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19
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20
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Vural A, Acar NP, Soylemezoglu F, Oguz KK, Dericioğlu N, Saka E. Isolated central nervous system Whipple's disease: Two cases. Clin Neurol Neurosurg 2015; 139:91-4. [PMID: 26407049 DOI: 10.1016/j.clineuro.2015.08.028] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2014] [Revised: 07/02/2015] [Accepted: 08/22/2015] [Indexed: 11/17/2022]
Abstract
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.
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Affiliation(s)
- Atay Vural
- Hacettepe University, Department of Neurology, Ankara, Turkey.
| | | | | | - Kader K Oguz
- Hacettepe University, Department of Radiology, Ankara, Turkey.
| | - Neşe Dericioğlu
- Hacettepe University, Department of Radiology, Ankara, Turkey
| | - Esen Saka
- Hacettepe University, Department of Neurology, Ankara, Turkey.
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21
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Zalonis I, Christidi F, Potagas C, Rentzos M, Evdokimidis I, Kararizou E. Central Nervous System Involvement as Relapse in Undiagnosed Whipple's Disease with Atypical Symptoms at Onset. Open Neurol J 2015; 9:21-3. [PMID: 26191089 PMCID: PMC4503830 DOI: 10.2174/1874205x01509010021] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2014] [Revised: 03/10/2015] [Accepted: 05/25/2015] [Indexed: 11/22/2022] Open
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.
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Affiliation(s)
- Ioannis Zalonis
- Department of Neurology, Aeginition Hospital, Medical School, Athens National & Kapodistrian University, 72-74 Vas. Sofias Avenue, Athens, 115 28, Greece
| | - Foteini Christidi
- Department of Neurology, Aeginition Hospital, Medical School, Athens National & Kapodistrian University, 72-74 Vas. Sofias Avenue, Athens, 115 28, Greece
| | - Constantin Potagas
- Department of Neurology, Aeginition Hospital, Medical School, Athens National & Kapodistrian University, 72-74 Vas. Sofias Avenue, Athens, 115 28, Greece
| | - Michalis Rentzos
- Department of Neurology, Aeginition Hospital, Medical School, Athens National & Kapodistrian University, 72-74 Vas. Sofias Avenue, Athens, 115 28, Greece
| | - Ioannis Evdokimidis
- Department of Neurology, Aeginition Hospital, Medical School, Athens National & Kapodistrian University, 72-74 Vas. Sofias Avenue, Athens, 115 28, Greece
| | - Evangelia Kararizou
- Department of Neurology, Aeginition Hospital, Medical School, Athens National & Kapodistrian University, 72-74 Vas. Sofias Avenue, Athens, 115 28, Greece
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22
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Abstract
Hepatic and gastrointestinal disorders can produce a wide spectrum of neurologic complications both affecting the central nervous system (CNS) and the peripheral nervous system. These manifestations range in severity from coma in acute liver failure and acute pancreatitis, to minor cognitive changes in chronic portosystemic encephalopathy and hepatitis C. Cerebrovascular diseases can complicate hepatitis C infection and inflammatory bowel disease. Demyelinating disorders may co-exist with inflammatory bowel disease. Anti-tumor necrosis factor alpha drugs may induce demyelination. Ataxia may occur in malabsorption syndromes and in gluten related disorders. Characteristic movement disorders are key features of acquired hepatocerebral degeneration and of Whipple disease. Multiple types of neuropathy can be found in association with hepatitis, inflammatory bowel disease and gluten related disorders.
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Affiliation(s)
- José M Ferro
- Department of Neurosciences, Service of Neurology, Hospital de Santa Maria, University of Lisbon, Av. Prof. Egas Moniz, 1649-035, Lisboa, Portugal,
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23
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Marth T. Systematic review: Whipple's disease (Tropheryma whipplei infection) and its unmasking by tumour necrosis factor inhibitors. Aliment Pharmacol Ther 2015; 41:709-24. [PMID: 25693648 DOI: 10.1111/apt.13140] [Citation(s) in RCA: 54] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2014] [Revised: 01/10/2015] [Accepted: 02/04/2015] [Indexed: 12/15/2022]
Abstract
BACKGROUND The classical form of Whipple's disease (WD), clinically characterised by arthropathy, diarrhoea and weight loss, is rare. Recently, other more frequent forms of Tropheryma whipplei infection have been recognised. The clinical spectrum includes an acute, self-limiting disease in children, localised forms affecting cardiac valves or the central nervous system without intestinal symptoms, and asymptomatic carriage of T. whipplei which is found in around 4% of Europeans. Genomic analysis has shown that T. whipplei represents a host-dependent or opportunistic bacterium. It has been reported that the clinical course of T. whipplei infection may be influenced by medical immunosuppression. AIM To identify associations between immunomodulatory treatment and the clinical course of T. whipplei infection. METHODS A PubMed literature search was performed and 19 studies reporting on immunosuppression, particularly therapy with tumour necrosis factor inhibitors (TNFI) prior to the diagnosis in 41 patients with Whipple?s disease, were evaluated. RESULTS As arthritis may precede the diagnosis of WD by many years, a relevant percentage (up to 50% in some reports) of patients are treated with immunomodulatory drugs or with TNFI. Many publications report on a complicated Whipple?s disease course or T. whipplei endocarditis following medical immunosuppression, particularly after TNFI. Standard diagnostic tests such as periodic acid-Schiff stain used to diagnose Whipple?s disease often fail in patients who are pre-treated by TNFI. CONCLUSIONS In cases of doubt, Whipple?s disease should be excluded before therapy with TNFI. The fact that immunosuppressive therapy contributes to the progression of T. whipplei infection expands our pathogenetic view of this clinical entity.
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Affiliation(s)
- T Marth
- Division of Internal Medicine, Krankenhaus Maria Hilf, Daun, Germany
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24
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Peregrin J, Malikova H. Primary Whipple disease of the brain: case report with long-term clinical and MRI follow-up. Neuropsychiatr Dis Treat 2015; 11:2461-9. [PMID: 26445540 PMCID: PMC4590553 DOI: 10.2147/ndt.s92066] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Whipple disease (WD) is a rare systemic disorder caused by the bacteria Tropheryma whipplei. In its classic form, it manifests with gastrointestinal problems including diarrhea, abdominal pain, and weight loss. However, various other systems can be affected, including the central nervous system (CNS). Even more rarely, the CNS is primarily affected without gastrointestinal symptoms and with a negative small bowel biopsy. The incidence of primary CNS WD is unknown. We report the case of a young female with the primary CNS form of WD. In this report, we highlight the main clinical features and diagnostic procedures that lead to the diagnosis and comment on the treatment and clinical response. We stress the importance of neuroimaging and brain biopsy. A unique feature of this case is that the patient has been followed up for 12 years. At the time of diagnosis, no neurological manifestations were detected, although a tumor-like lesion in the right temporal lobe and hypothalamic infiltration were present on magnetic resonance imaging (MRI). The first neurological manifestations developed 2 years later despite recommended antibiotic treatment, with cognitive impairment developing more than 10 years later. According to the MRI findings and clinical course, the disease was active for several years when multiple lesions on MRI appeared despite antibiotic therapy. In the discussion, we compare the present case with similar cases previously reported and we elaborate on the similarities and discrepancies in clinical features, diagnostic procedures, results, and treatment options.
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Affiliation(s)
- Jan Peregrin
- Department of Neurology, Charles University, Prague, Czech Republic
| | - Hana Malikova
- Department of Radiology, Na Homolce Hospital, Charles University, Prague, Czech Republic ; Second Faculty of Medicine, Institute of Anatomy, Charles University, Prague, Czech Republic
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25
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Infektionen. NEUROINTENSIV 2015. [PMCID: PMC7175474 DOI: 10.1007/978-3-662-46500-4_32] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
In diesem Kapitel werden zunächst die für die Neurointensivmedizin wesentlichen bakteriellen Infektionen (Meningitis, spinale und Hirnabszesse, Spondylodiszitis, septisch-embolische Herdenzephalitis) abgehandelt, die trotz gezielt eingesetzter Antibiotika und neurochirurgischer Therapieoptionen noch mit einer erheblichen Morbidität und Mortalität behaftet sind. Besonderheiten wie neurovaskuläre Komplikationen, die Tuberkulose des Nervensystems, Neuroborreliose, Neurosyphilis und opportunistische Infektionen bei Immunsuppressionszuständen finden hierbei besondere Berücksichtigung. Der zweite Teil dieses Kapitels behandelt akute und chronische Virusinfektionen des ZNS sowie in einem gesonderten Abschnitt die HIVInfektion und HIV-assoziierte Krankheitsbilder sowie Parasitosen und Pilzinfektionen, die in Industrieländern seit Einführung der HAART bei HIV zwar eher seltener, aber mit zunehmender Globalisierung auch in unseren Breiten immer noch anzutreffen sind.
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26
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Baizabal-Carvallo JF, Cardoso F, Jankovic J. Myorhythmia: Phenomenology, etiology, and treatment. Mov Disord 2014; 30:171-9. [DOI: 10.1002/mds.26093] [Citation(s) in RCA: 73] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2014] [Revised: 10/28/2014] [Accepted: 11/01/2014] [Indexed: 11/08/2022] Open
Affiliation(s)
- José Fidel Baizabal-Carvallo
- Parkinson's Disease Center and Movement Disorders Clinic; Department of Neurology; Baylor College of Medicine; Houston Texas USA
| | - Francisco Cardoso
- Movement Disorders Clinic; Neurology Service; Department of Internal Medicine; The Federal University of Minas Gerais; Belo Horizonte MG Brazil
| | - Joseph Jankovic
- Parkinson's Disease Center and Movement Disorders Clinic; Department of Neurology; Baylor College of Medicine; Houston Texas USA
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27
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Weidauer S, Nichtweiss M, Hattingen E. Differential diagnosis of white matter lesions: Nonvascular causes-Part II. Clin Neuroradiol 2014; 24:93-110. [PMID: 24519493 DOI: 10.1007/s00062-013-0267-1] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2013] [Accepted: 10/17/2013] [Indexed: 12/29/2022]
Abstract
The knowledge of characteristic lesion patterns is important in daily practice imaging, as the radiologist increasingly is required to provide precise differential diagnosis despite unspecific clinical symptoms like cognitive impairment and missed elaborated neurological workup. This part II dealing with nonvascular white matter changes of proven cause and diagnostic significance aimed to assist the evaluation of diseases exhibiting lesions exclusively or predominantly located in the white matter. The etiologies commented on are classified as follows: (a) toxic-metabolic, (b) leukodystrophies and mitochondriopathies, (c) infectious, (d) neoplastic, and (e) immune mediated. The respective mode of lesion formation is characterized, and typical radiological findings are displayed. More or less symmetrical lesion patterns on the one hand as well as focal and multifocal ones on the other are to be analyzed with reference to clinical data and knowledge of predilection sites characterizing major disease categories. Complementing spinal cord imaging may be useful not only in acute and relapsing demyelinating diseases but in certain leukodystrophies as well. In neuromyelitis optica (NMO), the detection of a specific antibody and some recently published observations may lead to a new understanding of certain deep white matter lesions occasionally complicating systemic autoimmune disease.
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Affiliation(s)
- S Weidauer
- Department of Neurology, Sankt Katharinen Hospital, Teaching Hospital of the Goethe University, Seckbacher Landstraße 65, 60389, Frankfurt am Main, Germany,
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Balasa M, Gelpi E, Rey MJ, Vila J, Ramió-Torrentà L, Quiles Granado AM, Molina Latorre R, Lepidi H, Raoult D, Saiz A. Clinical and neuropathological variability in clinically isolated central nervous system Whipple's disease. Brain Pathol 2014; 24:230-8. [PMID: 24320005 DOI: 10.1111/bpa.12113] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2013] [Accepted: 12/04/2013] [Indexed: 12/17/2022] Open
Abstract
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.
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Affiliation(s)
- Mircea Balasa
- Neurology Department, Hospital Clinic and Institut d'Investigació Biomèdica August Pi I Sunyer (IDIBAPS), Barcelona, Spain
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Compain C, Sacre K, Puéchal X, Klein I, Vital-Durand D, Houeto JL, De Broucker T, Raoult D, Papo T. Central nervous system involvement in Whipple disease: clinical study of 18 patients and long-term follow-up. Medicine (Baltimore) 2013; 92:324-330. [PMID: 24145700 PMCID: PMC4553994 DOI: 10.1097/md.0000000000000010] [Citation(s) in RCA: 58] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Whipple disease (WD) is a rare multisystemic infection with a protean clinical presentation. The central nervous system (CNS) is involved in 3 situations: CNS involvement in classic WD, CNS relapse in previously treated WD, and isolated CNS infection. We retrospectively analyzed clinical features, diagnostic workup, brain imaging, cerebrospinal fluid (CSF) study, treatment, and follow-up data in 18 patients with WD and CNS infection. Ten men and 8 women were included with a median age at diagnosis of 47 years (range, 30-56 yr). The median follow-up duration was 6 years (range, 1-19 yr). As categorized in the 3 subgroups, 11 patients had classic WD with CNS involvement, 4 had an isolated CNS infection, and 3 had a neurologic relapse of previously treated WD. CNS involvement occurred during prolonged trimethoprim-sulfamethoxazole (TMP-SMX) treatment in 1 patient with classic WD. The neurologic symptoms were various and always intermingled, as follows: confusion or coma (17%) related to meningo-encephalitis or status epilepticus; delirium (17%); cognitive impairment (61%) including memory loss and attention defects or typical frontal lobe syndrome; hypersomnia (17%); abnormal movements (myoclonus, choreiform movements, oculomasticatory myorhythmia) (39%); cerebellar ataxia (11%); upper motor neuron (44%) or extrapyramidal symptoms (33%); and ophthalmoplegia (17%) in conjunction or not with progressive supranuclear palsy. No specific pattern was correlated with any subgroup. Brain magnetic resonance imaging (MRI) revealed a unique focal lesion (35%), mostly as a tumorlike brain lesion, or multifocal lesions (23%) involving the medial temporal lobe, midbrain, hypothalamus, and thalamus. Periventricular diffuse leukopathy (6%), diffuse cortical atrophy (18%), and pachymeningitis (12%) were observed. The spinal cord was involved in 2 cases. MRI showed ischemic sequelae at diagnosis or during follow-up in 4 patients. Brain MRI was normal despite neurologic symptoms in 3 cases. CSF cytology was normal in 62% of patients, whereas Tropheryma whipplei polymerase chain reaction (PCR) analysis was positive in 92% of cases with tested CSF. Periodic acid-Schiff (PAS)-positive cells were identified in cerebral biopsies of 4 patients. All patients were treated with antimicrobial therapy for a mean duration of 2 years (range, 1-7 yr) with either oral monotherapy (TMP-SMX, doxycycline, third-generation cephalosporins) or a combination of antibiotics that sometimes followed parenteral treatment with beta-lactams and aminoglycosides. Eight patients also received hydroxychloroquine. At the end of follow-up, the clinical outcome was favorable in 14 patients (78%), with mild to moderate sequelae in 9. Thirteen patients (72%) had stopped treatment for an average time of 4 years (range, 0.7-14 yr). Four patients had clinical worsening despite antimicrobial therapy; 2 of those died following diffuse encephalitis (n = 1) and lung infection (n = 1). In conclusion, the neurologic manifestations of WD are diverse and may mimic almost any neurologic condition. Brain involvement may occur during or after TMP-SMX treatment. CSF T. whipplei PCR analysis is a major tool for diagnosis and may be positive in the absence of meningitis. Immune reconstitution syndrome may occur in the early months of treatment. Late prognosis may be better than previously reported, as a consequence of earlier diagnosis and a better use of antimicrobial therapy, including hydroxychloroquine and doxycycline combination.
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Affiliation(s)
- Caroline Compain
- From the Service de Médecine Interne (CC, KS, TP) and Service de Radiologie (IK), Université Paris Diderot, Assistance Publique des Hôpitaux de Paris (AP-HP), Hôpital Bichat, Paris; INSERM U699, (KS) Université Paris Diderot, Paris; Centre de Référence National sur les Vascularites Systémiques (XP), Université Paris-Descartes, Assistance Publique des Hôpitaux de Paris (AP-HP), Hôpital Cochin, Paris; Service de Médecine Interne (DV-D), Université Lyon-Sud, Lyon; Service de Neurologie (J-LH), Université Poitiers, Poitiers; Service de Neurologie (TDB), Hôpital de Saint-Denis, Saint Denis; Aix Marseille Université (DR), URMITE, UM63, CNRS 7278, IRD 198, INSERM 1095, Marseille, France
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Lagier JC, Fenollar F, Koric L, Guedj E, Ceccaldi M, Raoult D. Prise de poids, démence et syndrome cérébelleux sensible à la doxycycline : un probable nouveau cas lié à T. whipplei. Rev Med Interne 2013; 34:641-4. [DOI: 10.1016/j.revmed.2012.12.006] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2012] [Revised: 11/13/2012] [Accepted: 12/11/2012] [Indexed: 10/26/2022]
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Sung VW, Lyerly MJ, Fallon KB, Bashir K. Isolated CNS Whipple disease with normal brain MRI and false-positive CSF 14-3-3 protein: a case report and review of the literature. Brain Behav 2012; 2:838-43. [PMID: 23170246 PMCID: PMC3500470 DOI: 10.1002/brb3.97] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2012] [Revised: 07/28/2012] [Accepted: 09/05/2012] [Indexed: 12/19/2022] Open
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.
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Affiliation(s)
- Victor W Sung
- Department of Neurology, University of Alabama at Birmingham Birmingham, Alabama
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32
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Infektionen. NEUROINTENSIV 2012. [PMCID: PMC7123678 DOI: 10.1007/978-3-642-16911-3_32] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Trotz Weiterentwicklung moderner Antibiotika in den letzten Jahren sind die Letalitätszahlen der bakteriellen (eitrigen) Meningitis weiterhin hoch; Überlebende haben häufig neurologische Residuen. Die ungünstigen klinischen Verläufe der bakteriellen Meningitis sind meist Folge intrakranieller Komplikationen, wie z. B. eines generalisierten Hirnödems, einer zerebrovaskulären arteriellen oder venösen Beteiligung oder eines Hydrozephalus.
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Isolated inctracranial Whipple's disease—Report of a rare case and review of the literature. J Neurol Sci 2011; 308:1-8. [DOI: 10.1016/j.jns.2011.05.029] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2011] [Accepted: 05/17/2011] [Indexed: 11/19/2022]
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