RESUMO
Whipple disease is a granulomatous infectious disease caused by Tropheryma whipplei. The bacteria accumulate within macrophages, preferentially in the intestinal mucosa. Disease manifestation seems to be linked to immunological abnormalities of macrophages. We describe a patient with cerebral Whipple disease who presented with changes in mental status, confusion, inverse sleep-wake cycle, bilateral ptosis and vertical gaze palsy. Endoscopic biopsy sampling revealed Whipple disease in the gastric antrum but not in the duodenum. Whole blood stimulation displayed reactivity to T. whipplei that was at the lower end of healthy controls while reactivity of duodenal lymphocytes was not diminished. We propose that in cases of neurological symptoms suspicious of Whipple disease with normal duodenal and jenunal findings, biopsy sampling should be extended to the gastric mucosa. The robust reactivity of duodenal lymphocytes may have prevented our patient from developing small bowel disease, whereas the impaired reactivity in peripheral blood lymphocytes might yet explain the bacterial spreading to the central nervous system leading to the rare case of predominant neurological symptoms without relevant systemic involvement.
Assuntos
Encefalopatias/microbiologia , Antro Pilórico/microbiologia , Doença de Whipple/complicações , Biópsia , Encefalopatias/complicações , Confusão/etiologia , Duodeno/microbiologia , Humanos , Linfócitos/microbiologia , Masculino , Pessoa de Meia-Idade , Paralisia/etiologia , Transtornos do Sono-Vigília/etiologiaRESUMO
Recent clinical and laboratory findings have substantially advanced our understanding of neuromyelitis optica (NMO) as a humorally mediated, autoimmune disorder. We report on a patient who suffered a first episode of transverse myelitis at the age of 6 months following diphtheria-pertussis-tetanus (DPT) vaccination which had therefore been considered suggestive of acute disseminated encephalomyelitis (ADEM). Fifteen years later, the further disease course revealed typical NMO meeting all diagnostic criteria. This development points to a broad clinical and temporal heterogeneity of NMO, with ADEM probably occurring in the context of a shared autoimmune diathesis. Despite therapy response following B-cell depletion by rituximab, positive NMO-IgG autoantibody status remained unchanged, whereas direct testing for anti-aquaporin-4 (AQP-4)-antibodies was negative throughout. Our findings challenge the pathogenic relevance of NMO-IgG and indicate a varying diagnostic value of testing for NMO-IgG and AQP-4-autoantibodies.
Assuntos
Doenças Desmielinizantes/diagnóstico , Vacina contra Difteria, Tétano e Coqueluche/efeitos adversos , Encefalomielite Aguda Disseminada/diagnóstico , Neuromielite Óptica/diagnóstico , Quadriplegia/etiologia , Adolescente , Cegueira/etiologia , Corpo Caloso/patologia , Quimioterapia Combinada , Encefalomielite Aguda Disseminada/tratamento farmacológico , Feminino , Seguimentos , Humanos , Imunossupressores/uso terapêutico , Imageamento por Ressonância Magnética , Mielite Transversa/diagnóstico , Mielite Transversa/tratamento farmacológico , Neuromielite Óptica/tratamento farmacológico , Lobo Parietal/patologiaRESUMO
T cell resistance towards apoptotic elimination by activation-induced cell death (AICD) might be a crucial pathogenic feature of multiple sclerosis (MS). Since the Bcl-2 family is critically involved in the regulation of apoptosis, we investigated the protein expression of Bcl-2, Bcl-X(L), and Bax in peripheral blood mononuclear cells (PBMC) of 23 MS patients and 29 control subjects. An in vitro model of AICD, which exemplifies the elimination of antigen-reactive T cells in vivo, was used as an indication of T cell susceptibility or resistance towards apoptosis. Increased expression of the survival factor Bcl-X(L), which directly correlated with a resistance towards AICD, was observed in peripheral immune cells of MS patients. In contrast to Bcl-X(L), no differences were found in the protein expression of Bcl-2 and Bax between patients and controls. Our data indicate that the anti-apoptotic factor Bcl-X(L), responsible for T cell resistance towards apoptosis, might be an important factor in the MS pathogenesis and a potential target for therapeutic intervention.
Assuntos
Esclerose Múltipla/imunologia , Esclerose Múltipla/patologia , Proteínas Proto-Oncogênicas c-bcl-2/genética , Linfócitos T/citologia , Adulto , Apoptose/imunologia , Sobrevivência Celular/imunologia , Feminino , Expressão Gênica/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas/genética , RNA Mensageiro/análise , Proteína X Associada a bcl-2 , Proteína bcl-XAssuntos
Antígenos/imunologia , Neoplasias do Tronco Encefálico/imunologia , Neoplasias do Tronco Encefálico/patologia , Encefalite/imunologia , Encefalite/patologia , Síndromes Paraneoplásicas do Sistema Nervoso/imunologia , Síndromes Paraneoplásicas do Sistema Nervoso/patologia , Adulto , Antígenos/líquido cefalorraquidiano , Neoplasias do Tronco Encefálico/líquido cefalorraquidiano , Encefalite/líquido cefalorraquidiano , Feminino , Humanos , Imageamento por Ressonância Magnética , Síndromes Paraneoplásicas do Sistema Nervoso/líquido cefalorraquidiano , Tomografia por Emissão de Pósitrons , Remissão Espontânea , Tomografia Computadorizada por Raios XRESUMO
Limbic encephalitis is an inflammatory disease of the central nervous system characterized by diverse neurologic symptoms including mnestic disturbances, hallucinations, and seizures as well as behavioral symptoms like depression, personality changes, and acute confusional states resembling dementia. Several antibodies have been described in the pathogenesis of limbic encephalitis. It is often a paraneoplastic syndrome associated with small cell lung cancer, breast cancer, or Hodgkin's lymphoma among others. Here, we report a patient with B-cell chronic lymphocytic leukemia (B-CLL), presenting with otherwise unexplained neurologic symptoms consistent with limbic encephalitis. Despite intensive diagnostic procedures, no causing agent could be identified. Pleocytosis consisting of T cells was detected in the cerebrospinal fluid (CSF). We initiated anti-B-cell therapy with Rituximab for B-CLL with quick and durable resolution of symptoms. We speculate that disruption of interaction between autoreactive T and malignant B cells is responsible for the therapeutic effect of Rituximab.
Assuntos
Anticorpos Antineoplásicos/imunologia , Antígenos de Neoplasias/imunologia , Neoplasias Embrionárias de Células Germinativas/imunologia , Proteínas do Tecido Nervoso/imunologia , Síndromes Paraneoplásicas do Sistema Nervoso/imunologia , Neoplasias Testiculares/imunologia , Idoso , Evolução Fatal , Humanos , Masculino , Neoplasias Embrionárias de Células Germinativas/complicações , Neoplasias Embrionárias de Células Germinativas/cirurgia , Neoplasias Testiculares/complicações , Neoplasias Testiculares/cirurgiaAssuntos
Encefalopatias/patologia , Trombose das Artérias Carótidas/complicações , Infecções por HIV/complicações , Adulto , Encefalopatias/etiologia , Trombose das Artérias Carótidas/terapia , Angiografia Cerebral/métodos , Infecções por HIV/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Fatores de RiscoAssuntos
Resistência à Proteína C Ativada/complicações , Síndrome Antifosfolipídica/complicações , Infarto Cerebral/etiologia , Resistência à Proteína C Ativada/genética , Adulto , Anticoagulantes/uso terapêutico , Síndrome Antifosfolipídica/genética , Infarto Cerebral/diagnóstico por imagem , Infarto Cerebral/tratamento farmacológico , Infarto Cerebral/patologia , Fator V/genética , Feminino , Humanos , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Substância Cinzenta Periaquedutal/diagnóstico por imagem , Substância Cinzenta Periaquedutal/patologia , Mutação Puntual , Radiografia , Tálamo/diagnóstico por imagem , Tálamo/patologiaAssuntos
Doenças do Nervo Abducente/imunologia , Infecções por Campylobacter/imunologia , Campylobacter jejuni , Gangliosidose GM1/imunologia , Doenças do Nervo Abducente/etiologia , Doenças do Nervo Abducente/microbiologia , Adulto , Anticorpos/metabolismo , Infecções por Campylobacter/complicações , Infecções por Campylobacter/microbiologia , Humanos , MasculinoAssuntos
Abscesso Encefálico/patologia , Listeriose/patologia , Miastenia Gravis/complicações , Idoso , Antibacterianos/uso terapêutico , Abscesso Encefálico/complicações , Abscesso Encefálico/tratamento farmacológico , Edema Encefálico/tratamento farmacológico , Edema Encefálico/patologia , Humanos , Listeriose/complicações , Listeriose/tratamento farmacológico , Imageamento por Ressonância Magnética , Masculino , Tomografia Computadorizada por Raios XRESUMO
We report a case of a 24-year-old man with a right thalamic germinoma that initially mimicked a granulomatous inflammation, compatible with neurosarcoidosis based on clinical symptoms, imaging results and histology of an endoscopically navigated biopsy. A second biopsy, prompted by clinical course, and performed openly from parieto-lateral revealed the underlying germinoma, obscured in the first biopsy by a granulomatous tissue response, particularly at the tumor edge. The present case highlights granulomatous inflammatory tissue response on the tumor edge of germinoma as a tumor-immanent diagnostic challenge. This diagnostic problem is aggravated by stereotactic and endoscopic approaches. We conclude that granulomatous inflammation in a specimen obtained by biopsy of a midline lesion should always be considered for the differential diagnosis of germinoma. Stereotactic and endoscopic surgery should sample several different target points within the lesion. Because of tumor heterogeneity of germinoma, the open biopsy approach is advantageous compared to endoscopic or stereotactic techniques for germinoma and should be considered if a germinoma is in the differential diagnosis and if allowed by the clinical situation.
Assuntos
Neoplasias Encefálicas/patologia , Endoscopia , Germinoma/patologia , Granuloma/patologia , Doenças Talâmicas/patologia , Adulto , Biópsia , Neoplasias Encefálicas/metabolismo , Diagnóstico Diferencial , Germinoma/metabolismo , Humanos , Imuno-Histoquímica , Imageamento por Ressonância Magnética , Masculino , Sarcoidose/patologia , Doenças Talâmicas/metabolismo , Tomografia Computadorizada por Raios XRESUMO
We report on a novel subtype of Creutzfeldt-Jakob disease with a single proteinase K-resistant prion protein fragment of about 6 kDa in Western blots of brain homogenates. Clinically this patient showed a progressive spastic disorder and dementia over 3 years. No mutation of the prion protein gene was found. Since this patient had received a blood transfusion, an iatrogenic cause, albeit unlikely, cannot be ruled out. Future studies will have to be attentive to small prion protein fragments, which may cause or be associated with unusual clinical disease that might possibly only be diagnosed by immunoblotting of brain homogenates.
Assuntos
Química Encefálica , Encéfalo/metabolismo , Síndrome de Creutzfeldt-Jakob/metabolismo , Fragmentos de Peptídeos/análise , Príons/análise , Idoso , Western Blotting , Encéfalo/patologia , Síndrome de Creutzfeldt-Jakob/genética , Síndrome de Creutzfeldt-Jakob/patologia , Feminino , Humanos , Imuno-Histoquímica , Fragmentos de Peptídeos/química , Reação em Cadeia da Polimerase , Proteínas Priônicas , Príons/química , Príons/genéticaRESUMO
We describe a 25-year-old male patient with primary diffuse leptomeningeal gliomatosis (PDLG) presenting with gait ataxia, positive Lhermitte's sign, double vision, and right abducens nerve palsy. Spinal magnetic resonance imaging showed extended intradural, extramedullary, contrast-enhancing masses with compression of the myelon. Spinal leptomeningeal biopsy revealed a pilocytic astrocytoma WHO grade I. Despite chemotherapy with vincristin and carboplatin, the patient died 2 months after admission. A thorough autopsy showed no evidence for primary neoplasms in brain, spine and optic nerve. Sequence analysis of tumor protein 53 gene (TP53) revealed a missense mutation in exon 5, and expression of phosphatase and tensin homolog (mutated in multiple advanced cancers 1) (PTEN) protein was not detected, which may have contributed to astrocytoma development. To our knowledge, this is the first definitive case of pilocytic astrocytoma presenting as PDLG.