RESUMEN
BACKGROUND AND PURPOSE: Flat panel detector CT in the angiography suite may be valuable for the detection of intracranial hematomas; however, abnormal contrast enhancement frequently mimics hemorrhage. We aimed to assess the accuracy of flat panel detector CT in detecting/excluding intracranial bleeding after endovascular stroke therapy and whether it was able to reliably differentiate hemorrhage from early blood-brain barrier disruption. MATERIALS AND METHODS: Seventy-three patients were included for retrospective evaluation following endovascular stroke therapy: 32 after stent-assisted thrombectomy, 14 after intra-arterial thrombolysis, and 27 after a combination of both. Flat panel CT images were assessed for image quality and the presence and type of intracranial hemorrhage and BBB disruption by 2 readers separately and in consensus. Follow-up by multisection head CT, serving as the reference standard, was evaluated by a single reader. RESULTS: Conventional head CT revealed intracranial hematomas in 12 patients (8 subarachnoid hemorrhages, 7 cases of intracerebral bleeding, 3 SAHs plus intracerebral bleeding). Image quality of flat panel detector CT was considered sufficient in all cases supratentorially and in 92% in the posterior fossa. Regarding detection or exclusion of intracranial hemorrhage, flat panel detector CT reached a sensitivity, specificity, positive and negative predictive values, and accuracy of 58%, 85%, 44%, 91%, and 81%, respectively. Maximum attenuation measurements were not valuable for the differentiation of hemorrhage and BBB disruption. CONCLUSIONS: Flat panel CT after endovascular stroke treatment was able to exclude the rare event of an intracranial hemorrhage with a high negative predictive value. Future studies should evaluate the predictive value of BBB disruptions in flat panel detector CT for the development of relevant hematomas.
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Angiografía Cerebral/métodos , Hemorragia Cerebral/diagnóstico por imagen , Medios de Contraste/efectos adversos , Accidente Cerebrovascular/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Adulto , Anciano , Barrera Hematoencefálica/diagnóstico por imagen , Barrera Hematoencefálica/patología , Hemorragia Cerebral/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Sensibilidad y Especificidad , Accidente Cerebrovascular/complicaciones , Trombectomía , Terapia Trombolítica/efectos adversos , Terapia Trombolítica/métodosRESUMEN
Recently, the disappearance of oligoclonal bands (OCBs) from the cerebrospinal fluid (CSF) of a few natalizumab-treated patients with multiple sclerosis (MS) has been reported. This is interesting since CSF-restricted OCB are believed to persist in MS. We pooled CSF data from 14 MS centers to obtain an adequate sample size for investigating the suspected changes in central nervous system (CNS)-restricted humoral immune activities in the context of natalizumab therapy. In a retrospective chart analysis, CSF parameters of blood-CSF barrier integrity and intrathecal IgG production from 73 natalizumab-treated MS patients requiring a diagnostic puncture for exclusion of progressive multifocal leukoencephalopathy were compared with CSF data obtained earlier in the course of disease before natalizumab therapy. At the time of repeat lumbar puncture, local IgG production (according to Reibergram) was significantly reduced (p < 0.0001) and OCB had disappeared in 16% of the patients. We therefore conclude that natalizumab therapy interferes with intrathecal antibody production at least in a significant number of patients.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Formación de Anticuerpos/efectos de los fármacos , Linfocitos B/inmunología , Inmunoglobulina G/líquido cefalorraquídeo , Esclerosis Múltiple/líquido cefalorraquídeo , Bandas Oligoclonales/líquido cefalorraquídeo , Adolescente , Adulto , Anciano , Linfocitos B/efectos de los fármacos , Femenino , Humanos , Inmunoglobulina G/inmunología , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple/inmunología , Natalizumab , Bandas Oligoclonales/efectos de los fármacos , Bandas Oligoclonales/inmunología , Estudios Retrospectivos , Adulto JovenRESUMEN
Identifying and designing physical systems for use as qubits, the basic units of quantum information, are critical steps in the development of a quantum computer. Among the possibilities in the solid state, a defect in diamond known as the nitrogen-vacancy (NV(-1)) center stands out for its robustness--its quantum state can be initialized, manipulated, and measured with high fidelity at room temperature. Here we describe how to systematically identify other deep center defects with similar quantum-mechanical properties. We present a list of physical criteria that these centers and their hosts should meet and explain how these requirements can be used in conjunction with electronic structure theory to intelligently sort through candidate defect systems. To illustrate these points in detail, we compare electronic structure calculations of the NV(-1) center in diamond with those of several deep centers in 4H silicon carbide (SiC). We then discuss the proposed criteria for similar defects in other tetrahedrally coordinated semiconductors.
Asunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/microbiología , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Meningitis Criptocócica/etiología , Síndrome de Inmunodeficiencia Adquirida/microbiología , Síndrome de Inmunodeficiencia Adquirida/patología , Adulto , Edema Encefálico/etiología , Edema Encefálico/microbiología , Cerebelo/microbiología , Cerebelo/patología , Humanos , Masculino , Meningitis Criptocócica/diagnóstico , Meningitis Criptocócica/patología , Coloración y EtiquetadoRESUMEN
BACKGROUND: Bacterial meningitis is an unusual first manifestation but a major complication of infective endocarditis. PATIENTS AND METHODS: We present three well documented cases of isolated bacterial meningitis in endocarditis. Against this background we review the literature. RESULTS: All patients presented with bacterial meningitis. Staphylococcus aureus was isolated in blood cultures of all patients, but was found only in the cerebrospinal fluid (CSF) of one patient. The underlying endocarditis was confirmed histologically in all three cases. Two patients recovered completely and one died. CONCLUSION: An extensive search for endocarditis is recommended in every case of an unusual isolate in bacterial meningitis whether it is isolated from blood or CSF.
Asunto(s)
Endocarditis Bacteriana/diagnóstico , Meningitis Bacterianas/diagnóstico , Infecciones por Pseudomonas/diagnóstico , Sepsis/diagnóstico , Infecciones Estafilocócicas/diagnóstico , Anciano , Antibacterianos , Diagnóstico Diferencial , Quimioterapia Combinada/uso terapéutico , Ecocardiografía Transesofágica/métodos , Endocarditis Bacteriana/complicaciones , Endocarditis Bacteriana/tratamiento farmacológico , Femenino , Estudios de Seguimiento , Humanos , Imagen por Resonancia Magnética/métodos , Meningitis Bacterianas/complicaciones , Meningitis Bacterianas/tratamiento farmacológico , Persona de Mediana Edad , Infecciones por Pseudomonas/complicaciones , Infecciones por Pseudomonas/tratamiento farmacológico , Medición de Riesgo , Sepsis/complicaciones , Sepsis/tratamiento farmacológico , Índice de Severidad de la Enfermedad , Infecciones Estafilocócicas/complicaciones , Infecciones Estafilocócicas/tratamiento farmacológico , Resultado del TratamientoRESUMEN
Infective endocarditis involves the brain in 20-40% of cases. The neurologic syndrome often is the presenting feature. The most frequent neurologic complication is cerebral ischemia. In these patients and those with intracranial hemorrhage, a heart murmur as well as systemic signs of inflammation point to endocarditis. The encephalopathy in endocarditis is mostly due to cerebral infarction. In bacterial meningitis and brain abscess an uncommon isolate arouses suspicion. The most important therapy is antibiotic treatment. Valve replacement improves outcome; in the acute phase of endocarditis, however, it is only necessary in a third of the patients. Neurologic complications interfere with the timing of the valve replacement. If it is urgently required, its risk is reasonable within 3 days after cerebral ischemia; if possible 2-4 weeks should be waited. Cases of successful valve replacement within 4 weeks after intracranial hemorrhage have been reported, but it is recommended to postpone it for 4-6 weeks. There are no data available for the other neurologic complications. Even today patients with endocarditis challenge the diagnostic and therapeutic capacity of various disciplines.
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Encefalopatías/diagnóstico , Encefalopatías/terapia , Endocarditis Bacteriana/diagnóstico , Endocarditis Bacteriana/terapia , Manejo de Atención al Paciente/métodos , Encefalopatías/etiología , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/etiología , Isquemia Encefálica/terapia , Endocarditis Bacteriana/complicaciones , Humanos , Hipoxia-Isquemia Encefálica/diagnóstico , Hipoxia-Isquemia Encefálica/etiología , Hipoxia-Isquemia Encefálica/terapiaRESUMEN
Streptococcus pneumoniae is the major cause of bacterial meningitis and it damages the hippocampus by inducing neuronal apoptosis. The blocking of caspases provides only partial protection in experimental meningitis, which suggests that there is an additional apoptotic pathway. A trigger of this pathway is the bacterium itself, as exposure of microglia or neurons to live pneumococci induces rapid apoptosis. In this study, apoptosis was not associated with the activation of caspases-1-10 and was not inhibited by z-VAD-fmk, a broad-spectrum caspase inhibitor. Rather, apoptosis was attributed to damage to mitochondria, which was followed by the release of apoptosis-inducing factor (AIF) from the mitochondria, large-scale DNA fragmentation, and hypodiploidy. Furthermore, intracytoplasmatic microinjection of AIF-specific antiserum markedly impaired pneumococcus-induced apoptosis. These findings indicate that AIF may play a central role in brain cell apoptosis and bacterial pathogenesis.
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Apoptosis , Flavoproteínas/fisiología , Proteínas de la Membrana/fisiología , Microglía/patología , Neuronas/patología , Streptococcus pneumoniae/fisiología , Animales , Factor Inductor de la Apoptosis , Encéfalo , Línea Celular , Núcleo Celular/química , Núcleo Celular/patología , ADN/metabolismo , Fragmentación del ADN , Diploidia , Flavoproteínas/metabolismo , Humanos , Proteínas de la Membrana/metabolismo , Meningitis Bacterianas/fisiopatología , Ratones , Microglía/microbiología , Mitocondrias/metabolismo , Mitocondrias/patología , Neuronas/microbiología , Infecciones Neumocócicas/fisiopatologíaRESUMEN
Although patient series of clinical, electrophysiological, or magnetic resonance imaging evidence for involvement of the central nervous system in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) have been published, the histological proof has never been reported. We present the case of a 46-year-old male patient who developed CIDP in his early 20s and who died of relapsing severe pneumonia. In late stages of the disease the patient presented visual loss and bilateral atrophy of the optic nerve. Neuropathological examination revealed severe peripheral neuropathy consistent with CIDP and central involvement with bilateral optic neuritis. This is the first case reporting CIDP and histologically proven optic neuritis.
Asunto(s)
Nervio Óptico/patología , Neuritis Óptica/patología , Nervios Periféricos/patología , Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante/patología , Axones/inmunología , Axones/patología , Enfermedad Crónica , Resultado Fatal , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Vaina de Mielina/inmunología , Vaina de Mielina/patología , Nervio Óptico/inmunología , Nervio Óptico/fisiopatología , Neuritis Óptica/etiología , Neuritis Óptica/fisiopatología , Nervios Periféricos/inmunología , Nervios Periféricos/fisiopatología , Neumonía/etiología , Neumonía/fisiopatología , Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante/complicaciones , Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante/fisiopatologíaRESUMEN
Central nervous system (CNS) infections caused by Streptococcus pneumoniae still have a disastrous outcome. Underlying immunological and CNS cellular events are largely enigmatic. We used pneumococcal cells walls (PCW) to investigate microglial responses as these cells are prominent sensors and effectors during neuropathological changes. PCW stimulation of mouse microglia in vitro evoked the release of the cyto- and chemokines, TNF-alpha, IL-6, IL-12, KC, MCP-1, MIP-1alpha, MIP-2 and RANTES as well as soluble TNF receptor II, a potential TNF-alpha antagonist. The release induction followed extremely steep dose-response relations, and short exposure periods (15 min) were already sufficient to trigger substantial responses. PCW signaling controlling the release depended on both p38 and p42/p44 (ERK2/ERK1) MAP kinase activities. The kinase inhibitor, tyrphostin AG126 prevented the PCW-inducible phosphorylation of p42/p44(MAPK), potently blocked cytokine release and drastically reduced the bioavailable TNF-alpha, since it only marginally affected the release of soluble TNF receptors. Moreover, in an in vivo model of pneumococcal meningitis, AG126 significantly attenuated the PCW-induced leukocyte influx to the cerebrospinal fluid. The findings imply that pneumococcal CNS infection can cause a rapid and massive microglial activation and that ERK/MAPK pathway(s) are potential targets for pharmacological interventions.
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Citocinas/biosíntesis , Inhibidores Enzimáticos/farmacología , Meningitis Neumocócica/inmunología , Microglía/inmunología , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Tirfostinos/farmacología , Animales , Pared Celular/inmunología , Células Cultivadas , Quimiocinas/biosíntesis , MAP Quinasa Quinasa 1 , MAP Quinasa Quinasa 2 , Masculino , Ratones , Microglía/efectos de los fármacos , Proteína Quinasa 1 Activada por Mitógenos/fisiología , Proteína Quinasa 3 Activada por Mitógenos , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Proteínas Quinasas Activadas por Mitógenos/fisiología , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Tirosina Quinasas/metabolismo , Ratas , Ratas Wistar , Receptores del Factor de Necrosis Tumoral/biosíntesis , Streptococcus pneumoniae/inmunología , Factor de Necrosis Tumoral alfa/biosíntesis , Proteínas Quinasas p38 Activadas por MitógenosRESUMEN
The present report describes immunopathological, radiologcal and serological characteristics of antibody-mediated demyelination in a multiple sclerosis (MS) case with the main findings: (1) immunoglobulin and complement deposits in areas of active demyelination accompanied by massive macrophage activation; (2) ring-enhancing lesions in T1-weighted MRI after gadolinium application; (3) high titers of serum anti-myelin antibodies; and (4) signs of macrophage activation in the serum. Plasmapheresis may be a successful treatment for the type of inflammatory demyelination shown in the present case.
Asunto(s)
Enfermedades Desmielinizantes/inmunología , Enfermedades Desmielinizantes/patología , Esclerosis Múltiple/inmunología , Esclerosis Múltiple/patología , Autoanticuerpos/sangre , Biomarcadores , Sistema Nervioso Central/diagnóstico por imagen , Sistema Nervioso Central/inmunología , Sistema Nervioso Central/patología , Enfermedades Desmielinizantes/diagnóstico por imagen , Femenino , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad , Esclerosis Múltiple/diagnóstico por imagen , Proteínas de la Mielina/inmunología , Plasmaféresis , RadiografíaRESUMEN
The major goal of this study was to compare mechanisms of the neuroprotective potential of 17 beta-estradiol in two models for oxidative stress-independent apoptotic neuronal cell death with that in necrotic neuronal cell death in primary neuronal cultures derived from rat hippocampus, septum, or cortex. Neuronal apoptosis was induced either by staurosporine or ethylcholine aziridinium (AF64A), as models for necrotic cell death glutamate exposure or oxygen-glucose deprivation (OGD) were applied. Long-term (20 hr) pretreatment (0.1 microm 17 beta-estradiol) was neuroprotective in apoptotic neuronal cell death induced by AF64A (40 microm) only in hippocampal and septal neuronal cultures and not in cortical cultures. The neuroprotective effect was blocked by the estrogen antagonists ICI 182,780 and tamoxifen and the phosphatidylinositol 3-kinase (PI3-K) inhibitor LY294002. In glutamate and OGD-induced neuronal damage, long-term pretreatment was not effective. In contrast, short-term (1 hr) pretreatment with 17 beta-estradiol in the dose range of 0.5-1.0 microm significantly reduced the release of lactate dehydrogenase and improved morphology of cortical cultures exposed to glutamate or OGD but was not effective in the AF64A model. Staurosporine-induced apoptosis was not prevented by either long- or short-term pretreatment. The strong expression of the estrogen receptor-alpha and the modulation of Bcl proteins by 17 beta-estradiol in hippocampal and septal but not in cortical cultures indicates that the prevention of apoptotic, but not of necrotic, neuronal cell death by 17 beta-estradiol possibly depends on the induction of Bcl proteins and the density of estrogen receptor-alpha.
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Apoptosis/efectos de los fármacos , Colina/análogos & derivados , Estradiol/farmacología , Necrosis , Neuronas/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Animales , Aziridinas/farmacología , Hipoxia de la Célula/efectos de los fármacos , Células Cultivadas , Corteza Cerebral/citología , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/metabolismo , Colina/farmacología , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/farmacología , Antagonistas de Estrógenos/farmacología , Receptor alfa de Estrógeno , Glucosa/deficiencia , Glucosa/metabolismo , Ácido Glutámico/toxicidad , Hipocampo/citología , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , L-Lactato Deshidrogenasa/metabolismo , Neuronas/citología , Neuronas/metabolismo , Inhibidores de las Quinasa Fosfoinosítidos-3 , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Ratas , Ratas Wistar , Receptores de Estrógenos/metabolismo , Tabique del Cerebro/citología , Tabique del Cerebro/efectos de los fármacos , Tabique del Cerebro/metabolismo , Estaurosporina/farmacología , Factores de TiempoRESUMEN
Several studies have suggested high predictive values of serum procalcitonin (PCT) for the discrimination of bacterial and viral meningitis in children and adults. Here, we report PCT serum concentrations in 12 adults suffering from bacterial meningitis. PCT on admission was normal ( < or = 500 pg/ml) in 3 and between 500 and 1,000 pg/ml in 2 patients without evidence of concurrent bacterial infections. Conversely, in 5 patients with PCT concentrations between 2,268 and 38,246 pg/ml other infections were present. PCT concentrations were higher with typical meningitis agents (pneumococci and meningococci 12,679 +/- 13,092 pg/ml vs. other bacteria 4048 +/- 9187 pg/ml, p = 0.041) whilst in nosocomial bacterial meningitis after neurosurgery (n = 3) serum PCT remained normal. We believe that PCT is of limited diagnostic value in adults suffering from bacterial meningitis, especially in cases due to unusual agents or of nosocomial origin. Elevated PCT in bacterial meningitis may indicate the presence of bacterial inflammation outside the central nervous system.
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Calcitonina/sangre , Meningitis Bacterianas/sangre , Precursores de Proteínas/sangre , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Proteína C-Reactiva/análisis , Péptido Relacionado con Gen de Calcitonina , Infección Hospitalaria/diagnóstico , Diagnóstico Diferencial , Femenino , Humanos , Recuento de Leucocitos , Masculino , Meningitis Bacterianas/diagnóstico , Meningitis Viral/sangre , Meningitis Viral/diagnóstico , Persona de Mediana Edad , Sensibilidad y EspecificidadRESUMEN
Headache as a cardinal symptom of acute meningitis reflects activation of trigeminal afferents from the meninges. With their perivascular endings, these fibers form the so-called trigeminovascular system (TVS), which releases proinflammatory neuropeptides upon nociceptive stimulation. In the present article, we review a role of the TVS in enhancing the early inflammatory response of bacterial meningitis. Furthermore, we discuss inhibition of neuropeptide release from the TVS using 5HT(1B/D) agonists as a potential new anti-inflammatory treatment strategy for early bacterial meningitis.
Asunto(s)
Meninges/irrigación sanguínea , Meningitis Bacterianas/fisiopatología , Inflamación Neurogénica/fisiopatología , Nervio Trigémino/fisiopatología , Vías Aferentes/fisiopatología , Animales , Cefalea/fisiopatología , Humanos , Meninges/fisiopatología , Neuropéptidos/antagonistas & inhibidores , Neuropéptidos/metabolismoRESUMEN
OBJECTIVE: To assess the survival rate and functional outcome in elderly patients with space occupying supratentorial infarction who underwent hemicraniectomy compared with those who received medical treatment alone. METHODS: All patients older than 55 years with space occupying middle cerebral artery (MCA) infarction treated in our clinic between January 1998 and July 1999 were included in this retrospective analysis. Patients were eligible for decompressive surgery if they were younger than 75 and had no severe comorbidity. Hemicraniectomy was performed regardless of the affected hemisphere. All patients were followed up for assessment of functional outcome; data were assessed according to the Barthel index and modified Rankin scale and cover a period of 3 to 9 months after infarction. RESULTS: Twelve out of 24 patients underwent hemicraniectomy. Eight patients who were operated on survived; only one patient died of transtentorial herniation, three other deaths were due to medical complications. None of the survivors had a Barthel score above 60 or a Rankin score below 4. Nine out of 12 medically treated patients died of transtentorial herniation, one patient died of medical complications. The two surviving patients had a Barthel score below 60 and a Rankin score of 4. CONCLUSIONS: Craniectomy in elderly patients with space occupying MCA infarction improves survival rates compared with medical treatment alone. However, functional outcome and level of independence are poor. Craniectomy in elderly patients should not be performed unless a prospective randomised trial proves beneficial.
Asunto(s)
Envejecimiento/fisiología , Encéfalo/cirugía , Infarto de la Arteria Cerebral Media/fisiopatología , Infarto de la Arteria Cerebral Media/cirugía , Anciano , Encéfalo/fisiopatología , Femenino , Humanos , Infarto de la Arteria Cerebral Media/mortalidad , Masculino , Persona de Mediana Edad , Análisis de SupervivenciaRESUMEN
To assess the neuroprotective potential of melatonin in apoptotic neuronal cell death, we investigated the efficacy of melatonin in serum-free primary neuronal cultures of rat cortex by using three different models of caspase-dependent apoptotic, excitotoxin-independent neurodegeneration and compared it to that in necrotic neuronal damage. Neuronal apoptosis was induced by either staurosporine or the neurotoxin ethylcholine aziridinium (AF64A) with a delayed occurrence of apoptotic cell death (within 72 h). The apoptotic component of oxygen-glucose deprivation (OGD) unmasked by glutamate antagonists served as a third model. As a model for necrotic cell death, OGD was applied. Neuronal injury was quantified by LDH release and loss of metabolic activity. Although melatonin (0.5 mM) partly protected cortical neurons from OGD-induced necrosis, as measured by a significant reduction in LDH release, it was not effective in all three models of apoptotic cell death. In contrast, exaggeration of neuronal damage by melatonin was observed in native cultures as well as after induction of apoptosis. The present data suggest that the neuroprotectiveness of melatonin strongly depends on the model of neuronal cell death applied. As demonstrated in three different models of neuronal apoptosis, the progression of the apoptotic type of neuronal cell death cannot be withhold or is even exaggerated by melatonin, in contrast to its beneficial effect in the necrotic type of cell death.
Asunto(s)
Apoptosis , Caspasas/metabolismo , Colina/análogos & derivados , Melatonina/farmacología , Neuronas/efectos de los fármacos , Tiourea/análogos & derivados , Animales , Antioxidantes/farmacología , Aziridinas , Inhibidores de Caspasas , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Óxidos N-Cíclicos , Interacciones Farmacológicas , Inhibidores Enzimáticos/farmacología , Depuradores de Radicales Libres/farmacología , Radicales Libres/metabolismo , Glucosa/deficiencia , Glucosa/metabolismo , Hipoxia/metabolismo , Necrosis , Neuronas/patología , Óxidos de Nitrógeno/farmacología , Ratas , Ratas Wistar , Estaurosporina/farmacología , Tiourea/farmacologíaAsunto(s)
Absceso/complicaciones , Alucinaciones/etiología , Alucinaciones/patología , Meningitis Bacterianas/complicaciones , Puente/microbiología , Absceso/patología , Humanos , Imagen por Resonancia Magnética , Masculino , Meningitis Bacterianas/patología , Persona de Mediana Edad , Música , Puente/patologíaRESUMEN
An 18-year-old woman was admitted to hospital because of subcutaneous hematoma and fever of unknown origin. Acute myeloid leukemia was diagnosed and empirical antimicrobial treatment and induction chemotherapy were started. After initial defervescence, fever relapsed 2 days after the onset of neutropenia. The CT scan of the lung was consistent with an invasive fungal infection. Treatment with amphotericin B was started and antimicrobial treatment was continued with liposomal amphotericin B because of an increase in creatinine later. The fever persisted and the patient suddenly developed progressive neurological symptoms. CT scan of the head suggested cerebral infarction and angiography of the extra- and intracranial arteries showed signs of vasculitis. Six days after the onset of neurological symptoms cerebral death was diagnosed. Autopsy revealed non-septate, irregularly branched hyphae in various histologic sections including brain. Absidia corymbifera could be isolated from lung tissue confirming the diagnosis of disseminated mucormycosis. In this case, angiographic findings suggested severe cerebral vasculitis which was in fact caused by thromboembolic dissemination of fungal hyphae. This case underlines the fact that cerebral symptoms in febrile neutropenic patients are highly indicative for fungal infections of the brain.
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Absidia , Mucormicosis/patología , Vasculitis del Sistema Nervioso Central/etiología , Absidia/aislamiento & purificación , Adolescente , Anfotericina B/uso terapéutico , Antifúngicos/uso terapéutico , Angiografía Cerebral , Resultado Fatal , Femenino , Fiebre/etiología , Hematoma , Humanos , Leucemia Mieloide Aguda/complicaciones , Pulmón/microbiología , Pulmón/patología , Mucormicosis/complicaciones , Neutropenia/complicaciones , Neutropenia/etiología , Tromboembolia/complicaciones , Tromboembolia/patología , Vasculitis del Sistema Nervioso Central/microbiologíaRESUMEN
The involvement of nitric oxide in neurodegenerative processes still remains incompletely characterized. Although nitric oxide has been reported to be an important mediator in neuronal degeneration in different models of cell death involving NMDA-receptor activation, increasing evidence for protective mechanisms has been obtained. In this study the role of nitric oxide was investigated in a model of NMDA-independent, delayed apoptotic cell death, induced by the neurotoxin ethylcholine aziridinium ethylcholine aziridinium both in vivo and in vitro. For the in vivo evaluation rats received bilateral intracerebroventricular injections of ethylcholine aziridinium (2nmol/ventricle) or vehicle. In the hippocampus a transient decrease in nitric oxide synthase activity occurred, reaching its lowest levels three days after ethylcholine aziridinium treatment (51.7+/-9.8% of controls). The decrease coincided with the maximal reduction in choline acetyltransferase activity as marker for the extent of cholinergic lesion. The effect of pharmacological inhibition of nitric oxide synthase was tested by application of various nitric oxide synthase inhibitors with different selectivity for the nitric oxide synthase-isoforms. Unspecific nitric oxide synthase inhibition resulted in a significant potentiation of the loss of choline acetyltransferase activity in the hippocampus measured seven days after ethylcholine aziridinium application, whereas the specific inhibition of neuronal or inducible nitric oxide synthase was ineffective. These pharmacological data are suggestive for a neuroprotective role of nitric oxide generated by endothelial nitric oxide synthase. In vitro experiments were performed using serum-free primary neuronal cell cultures from hippocampus, cortex and septum of E15-17 Wistar rat embryos. Ethylcholine aziridinium-application in a range of 5-80microM resulted in delayed apoptotic neurodegeneration with a maximum after three days as confirmed by morphological criteria, life-death assays and DNA laddering. Nitric oxide synthase activity in harvested cells decreased in a dose- and time-dependent manner. Nitric oxide production as determined by measurement of the accumulated metabolite nitrite in the medium was equally low in controls and in ethylcholine aziridinium treated cells (range 0.77-1.86microM nitrite). An expression of inducible nitric oxide synthase messenger RNA could not be detected by semiquantitative RT-PCR 13h after ethylcholine aziridinium application. The present data indicate that in a model of delayed apoptotic neurodegeneration as induced by ethylcholine aziridinium neuronal cell death in vitro and in vivo is independent of the cytotoxic potential of nitric oxide. This is confirmed by a decrease in nitric oxide synthase activity, absence of nitric oxide production and absence of inducible nitric oxide synthase expression. In contrast, evidence for a neuroprotective role of nitric oxide was obtained in vivo as indicated by the exaggeration of the cholinergic lesion after unspecific nitric oxide synthase inhibition by N-nitro-L-arginine methylester.