RESUMEN
Malaria continues to be a major global health problem, and over 40% of the world's population is at risk. Severe or complicated malaria is defined by clinical or laboratory evidence of vital organ dysfunction, including dysfunction of the central nervous system (CNS). The pathogenesis of complicated malaria has not been completely elucidated; however, the development of the multiorgan affection seems to play an important role in the disruption of the blood brain barrier (BBB) that protects the CNS against chemical insults. Historically, the BBB has received more attention in the pathogenesis of malaria than have the cerebrospinal fluid-brain barrier (CSFBB) and ependymal cells. This perspective may be misguided because, in the context of disease or toxicity, the CSFBB is more vulnerable to many foreign invaders than are the capillaries. Given the lack on studies of the damage to the CSFBB and ependymal epithelium in experimental murine malaria, the present study evaluated morphological changes in the ependymal cells of CD-1 male mice infected with lethal Plasmodium yoelii yoelii (Pyy) via histopathology and scanning electron microscopy (SEM). Samples were taken two, four and six days post-infection (PI). No lesions were observed upon the initial infection. By the fourth day PI, fourth ventricle ependymal samples exhibited disruptions and roughened epithelia. More severe injuries were observed at six days PI and included thickened cilia and deep separations between the ependymal intercellular spaces. In some of the analyzed areas, the absence of microvilli and cell layer detachment were observed, and some areas exhibited blebbing surfaces. The ependymal cell lesions observed in the CD1 male mice infected with lethal Pyy seemed to facilitate the paracellular permeability of the CSFBB and consequently promote the access of inflammatory mediators and toxic molecules through the barrier, which resulted in damage to the brain tissue. Understanding the mechanism of ependymal disruption during lethal murine malaria could help to elucidate the local and systemic factors that are involved in the pathogenesis of the disease and may provide essential clues for the prevention and treatment of complicated human malaria.
Asunto(s)
Epéndimo/patología , Malaria/patología , Plasmodium yoelii , Animales , Barrera Hematoencefálica/parasitología , Barrera Hematoencefálica/patología , Encéfalo/parasitología , Encéfalo/patología , Recuento de Células , Ventrículos Cerebrales/parasitología , Ventrículos Cerebrales/patología , Malaria/parasitología , Masculino , Mesencéfalo/parasitología , Mesencéfalo/patología , RatonesRESUMEN
We describe a patient presenting with vertical one-and-a-half syndrome and concomitant contralesional horizontal gaze paresis as the result of a solitary neurocysticercosis (NCC) lesion in the right midbrain extending into the thalamomesencephalic junction. The patient received an albendazole-dexamethasone course which resulted in resolution of his symptoms. The neuro-ophthalmological complications of NCC are reviewed and the clinical topography of the neuro-ophthalmological findings of this unusual observation are discussed.
Asunto(s)
Diplopía/etiología , Neurocisticercosis/complicaciones , Nistagmo Patológico/etiología , Trastornos de la Motilidad Ocular/etiología , Enfermedades del Nervio Oculomotor/etiología , Enfermedades del Nervio Abducens/diagnóstico , Adulto , Albendazol/uso terapéutico , Antihelmínticos/uso terapéutico , Blefaroptosis/etiología , Dexametasona/uso terapéutico , Diagnóstico Diferencial , Diplopía/tratamiento farmacológico , Quimioterapia Combinada , Cefalea/etiología , Humanos , Masculino , Mesencéfalo/parasitología , Mesencéfalo/fisiopatología , Neurocisticercosis/diagnóstico , Neurocisticercosis/tratamiento farmacológico , Neurocisticercosis/fisiopatología , Nistagmo Patológico/tratamiento farmacológico , Trastornos de la Motilidad Ocular/tratamiento farmacológico , Enfermedades del Nervio Oculomotor/diagnóstico , Enfermedades del Nervio Oculomotor/tratamiento farmacológico , Enfermedades del Nervio Oculomotor/parasitología , Reflejo Anormal , Tálamo/parasitología , Tálamo/fisiopatologíaRESUMEN
Isolated ptosis is a rare presentation of neurocysticercosis (NCC). Here we report the case of a 45-year-old woman who presented with acute onset bilateral symmetrical ptosis with no other neurological deficit. Her imaging revealed a single cystic ring-enhancing lesion with perilesional oedema in the midbrain suggestive of NCC. She responded well to prednisolone.
Asunto(s)
Albendazol/uso terapéutico , Antihelmínticos/uso terapéutico , Blefaroptosis/parasitología , Mesencéfalo/parasitología , Neurocisticercosis/diagnóstico , Prednisolona/uso terapéutico , Animales , Diagnóstico Diferencial , Femenino , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad , Neurocisticercosis/complicaciones , Neurocisticercosis/tratamiento farmacológico , Resultado del TratamientoRESUMEN
Brainstem alone is involved very infrequently in patients with neurocysticercosis; usually, it occurs in association with disseminated form of the disease. Isolated involvement of the third nerve is commonly due to vascular causes. We are reporting a case due to cysticercus lesion presenting as isolated third-nerve involvement with sparing of the pupil. The diagnosis of neurocysticercosis was established by the presence of characteristic granulomatous lesions in the midbrain along with positive ELISA for cysticercal antigen in the cerebrospinal fluid. The patient responded well to corticosteroids with almost complete recovery. A follow-up MRI scan showed a significant decrease in the size of the lesion.
Asunto(s)
Mesencéfalo/parasitología , Neurocisticercosis/complicaciones , Enfermedades del Nervio Oculomotor/parasitología , Taenia solium/aislamiento & purificación , Animales , Diagnóstico Diferencial , Humanos , Masculino , Mesencéfalo/patología , Neurocisticercosis/tratamiento farmacológico , Neurocisticercosis/patología , Enfermedades del Nervio Oculomotor/tratamiento farmacológico , Enfermedades del Nervio Oculomotor/patología , Adulto JovenRESUMEN
Neurocysticercosis is the most common parasitic infestation of the central nervous system, which manifests commonly as acute-onset focal seizures. We report a rare nonepileptic manifestation of neurocysticercosis: midbrain neurocysticercosis presenting as sudden-onset ptosis in 2 children. To our knowledge, this has not been reported previously in children.
Asunto(s)
Blefaroptosis/etiología , Encefalopatías/complicaciones , Mesencéfalo/parasitología , Neurocisticercosis/complicaciones , Neurocisticercosis/tratamiento farmacológico , Enfermedad Aguda , Albendazol/uso terapéutico , Antihelmínticos/uso terapéutico , Antiinflamatorios/uso terapéutico , Blefaroptosis/parasitología , Encefalopatías/diagnóstico por imagen , Encefalopatías/parasitología , Encefalopatías/fisiopatología , Niño , Preescolar , Femenino , Humanos , Masculino , Mesencéfalo/diagnóstico por imagen , Mesencéfalo/fisiopatología , Neurocisticercosis/diagnóstico por imagen , Prednisolona/uso terapéutico , Radiografía , Resultado del TratamientoRESUMEN
Outbred CD1 mice were administered doses of 1000 and 3000 Toxocara canis eggs and postmortem took place on days 7, 42 and 120 post-infection. Mice were killed by cervical dislocation and brains were sagitally bisected and fixed in 10% neutral buffered formalin prior to histological preparation and examination. The number of T. canis larvae were counted per brain and per section and the number of larvae cited for the first time per section were also recorded. These observations were compared by dose administered and by day of postmortem. The total number of larvae per brain and per section was higher for the 3000 dose compared to the 1000 dose. A different pattern emerged for the number of larvae observed in the brain over the three postmortem days depending upon the dose received. For the 1000 dose larval numbers increase from day 7 to day 120 whereas for the 3000 dose the opposite trend occurs. Larvae were assigned to one of five regions in the brain - the telencephalon, diencephalon, cerebellum, medulla, pons and brain stem and the olfactory bulb. Larvae did not show a random distribution in the brain. The majority of larvae were recorded from the telencephalon and the cerebellum. The percentage of sections with larvae in them is higher for the 3000 dose compared to the 1000 dose for all regions of the brain. For the majority of regions, the percentage of sections with larvae in them increases between day 7 and 42 and then decreases by day 120 and this is most pronounced for the cerebellum. For the telencephalon and diencephalon only, more larvae were detected on the right hand side of the brain compared to the left hand side. Statistical analysis revealed that dose and brain region are significant factors which influence the number of larvae observed in histological sections of the brain but day post-infection is not.
Asunto(s)
Encéfalo/parasitología , Toxocara canis/aislamiento & purificación , Toxocariasis/parasitología , Análisis de Varianza , Animales , Cerebelo/parasitología , Distribución de Chi-Cuadrado , Diencéfalo/parasitología , Larva , Masculino , Bulbo Raquídeo/parasitología , Mesencéfalo/parasitología , Ratones , Bulbo Olfatorio/parasitología , Telencéfalo/parasitología , Factores de TiempoRESUMEN
We have characterized brain cytokine expression profiles in the Plasmodium coatneyi/rhesus (Macaque mulatta) malaria model. Eight rhesus monkeys were included in the study; four were infected with P. coatneyi, and four were used as uninfected controls. All inoculated animals became infected. Eleven days after parasite inoculation, the rhesus monkeys were killed and tissue samples from 4 regions of the brain (cortex and white matter of the cerebrum, cerebellum, and midbrain) were collected for quantitation of mRNA expression of cytokines, adhesion molecules, and inducible nitric oxide synthetase (iNOS) by reverse transcriptase-polymerase chain reaction (RT-PCR). The expression levels of tumor necrosis actor-alpha (TNF-alpha), gamma interferon (IFN-gamma), interleukin-1-beta (IL-1beta), intercellular adhesion molecule-1 (ICAM-1) and inducible nitric oxide synethetase (iNOS) were highest in the cerebellum of infected animals, correlating well with pathologic observations of sequestration of parasitized erythrocytes in this region of the brain. Infected animals also had higher TNF-alpha expression levels in the cortex and IL-1beta expression levels in the cortex, white matter, and midbrain. Thus, the expression of pro-inflammatory and T helper-1 (TH-1) cytokines, adhesion molecules, and iNOS appears to predominate in the cerebellum of infected rhesus monkeys.
Asunto(s)
Encéfalo/inmunología , Citocinas/genética , Malaria/inmunología , Animales , Encéfalo/irrigación sanguínea , Encéfalo/parasitología , Cerebelo/irrigación sanguínea , Cerebelo/inmunología , Cerebelo/parasitología , Corteza Cerebral/irrigación sanguínea , Corteza Cerebral/inmunología , Corteza Cerebral/parasitología , Citocinas/metabolismo , Modelos Animales de Enfermedad , Expresión Génica , Molécula 1 de Adhesión Intercelular/genética , Molécula 1 de Adhesión Intercelular/metabolismo , Interferón gamma/genética , Interferón gamma/metabolismo , Interleucina-1/genética , Interleucina-1/metabolismo , Interleucina-12/genética , Interleucina-12/metabolismo , Macaca mulatta , Mesencéfalo/irrigación sanguínea , Mesencéfalo/inmunología , Mesencéfalo/parasitología , Microcirculación/parasitología , Óxido Nítrico Sintasa/genética , Óxido Nítrico Sintasa/metabolismo , Óxido Nítrico Sintasa de Tipo II , Parasitemia/inmunología , ARN Mensajero/metabolismo , Telencéfalo/irrigación sanguínea , Telencéfalo/inmunología , Telencéfalo/parasitología , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Cerebral malaria is a fatal complication of infection by Plasmodium falciparum in man. The neurological symptoms that characterize this form of malarial disease are accompanied by the adhesion of infected erythrocytes to the vasculature of the brain. To study this phenomenon in vivo, an acute phase severe combined immunodeficiency (SCID) mouse model was developed in which sequestration of P. falciparum-infected human erythrocytes took place. During acute cerebral malaria in humans, the expression of intercellular adhesion molecule-1 (ICAM-1) is induced in vascular endothelium by inflammatory reactions. Acute phase ICAM-1 expression can also be obtained in SCID mice. The endothelium of the midbrain region was the most responsive to such inflammatory stimulus. It is noteworthy that the reticular formation in the midbrain controls the level of consciousness, and loss of consciousness is a symptom of cerebral malaria. We found that infected human erythrocytes were retained 24 times more than normal erythrocytes in ICAM-1-positive mouse brain. Sequestration to the brain was reduced by anti-ICAM-1 antibodies. These in vivo results were confirmed by the binding of P. falciparum-infected erythrocytes to the ICAM-1-positive endothelium in tissue sections of mouse brain. We conclude that the SCID mouse serves as a versatile in vivo model that allows the study of P. falciparum-infected erythrocyte adhesion as it occurs in human cerebral malaria. Upregulation of ICAM-1 expression in the region of the midbrain correlates with increased retention of malaria-infected erythrocytes and with the symptoms of cerebral malaria.
Asunto(s)
Eritrocitos/parasitología , Malaria Cerebral/sangre , Malaria Falciparum/sangre , Ratones SCID/parasitología , Plasmodium falciparum/fisiología , Animales , Secuencia de Bases , Adhesión Celular , Endotelio Vascular/fisiopatología , Femenino , Interacciones Huésped-Parásitos , Molécula 1 de Adhesión Intercelular/genética , Molécula 1 de Adhesión Intercelular/fisiología , Células L , Pulmón/parasitología , Malaria Cerebral/complicaciones , Malaria Cerebral/parasitología , Malaria Falciparum/complicaciones , Malaria Falciparum/parasitología , Mesencéfalo/parasitología , Ratones , Ratones Endogámicos BALB C , Ratones SCID/sangre , Datos de Secuencia Molecular , Proteínas Recombinantes/metabolismo , Inmunodeficiencia Combinada Grave/complicaciones , Organismos Libres de Patógenos Específicos , TransfecciónRESUMEN
A subspecies of Naegleria australiensis, N. australiensis italica, pathogenic for mice, was recently isolated and identified from an Italian thermal spa. We describe the histopathological changes of the central nervous system with experimental infection of albino mice. The histopathological patterns are intermediate to those seen with infection caused by N. fowleri and N. australiensis or Acanthamoeba spp. An acute inflammatory reaction was present within the choroid plexus, ependyma, midbrain, cerebellum, and basal ganglia. Occasional single amebic trophozoites were found within some microabscesses. Cysts were not identified. Involvement of the olfactory neuroepithelium and of the nasal mucosa was not detected.