RESUMEN
INTRODUCTION: Malignant intracranial ependymomas in childhood have a poor prognosis, supratentorial ependymomas have the poorest clinical course with a survival rate after 5 years of 45%. The most important prognostic factor in these cases is a radical operation, which cannot usually, however, prevent relapse. CASE REPORT: We demonstrate the case of a large malignant ependymoma of the left cerebral hemisphere in a child who has so far lived for 16 years without relapse after an extensive but uncomplicated left-sided hemispherectomy. The patient has also shown an improvement in her preoperative neurologic deficits. Her epilepsy, which was difficult to manage preoperatively, has been completely eliminated. She went to a special school for handicapped children and now works there. She does not need any help in handling everyday activities. CONCLUSION: This case shows the significance of complete tumor resection in malignant ependymomas, which may, under certain circumstances, lead to lasting tumor control.
Asunto(s)
Ependimoma/cirugía , Hemisferectomía/métodos , Neoplasias Supratentoriales/cirugía , Femenino , Humanos , Lactante , Estudios Longitudinales , Imagen por Resonancia Magnética/métodos , Coloración y Etiquetado/métodos , Neoplasias Supratentoriales/patología , Tomografía Computarizada por Rayos X/métodos , Resultado del TratamientoRESUMEN
Multidrug resistance proteins (MRPs, symbol ABCC) are membrane glycoproteins that mediate the ATP-dependent export of organic anions, including cytotoxic and antiviral drugs, from cells. To identify MRP family members possibly involved in the intrinsic resistance of human brain to cytotoxic and antiviral drugs, we analyzed the expression and localization of MRP1-MRP6 in rapidly frozen perilesional samples of several regions of adult human brain obtained during neurosurgery. Quantitative polymerase chain reaction analysis showed expression of MRP1, MRP2, MRP3, MRP4, and MRP5 mRNA, whereas MRP6 mRNA was below detectability. However, immunofluorescence microscopy of cryosections from human brain showed no reactivity for the MRP2 or MRP3 proteins. The proteins MRP1, MRP4, and MRP5 were clearly localized by confocal laser scanning microscopy to the luminal side of brain capillary endothelial cells. The MRP4 and MRP5 proteins were also detected in astrocytes of the subcortical white matter. Notably, MRP5 protein was present in pyramidal neurons. MRP proteins may, thus, contribute to the cellular efflux of endogenous anionic glutathione or glucuronate conjugates (substrates for MRP1), cyclic nucleotides (substrates for MRP4 and MRP5), or glutathione (co-substrate for MRP1 and MRP4); in addition, they may play an important role in the resistance of the brain to several cytotoxic and antiviral drugs.
Asunto(s)
Transportadoras de Casetes de Unión a ATP/biosíntesis , Química Encefálica/fisiología , Genes MDR/genética , Astrocitos/metabolismo , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/cirugía , Corteza Cerebral/citología , Corteza Cerebral/metabolismo , Hemorragia Cerebral/metabolismo , Glioma/metabolismo , Glioma/cirugía , Humanos , Inmunohistoquímica , Microscopía Fluorescente , Células Piramidales/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
A graph method was employed to analyze the spatial neuronal patterns of nuclear grays of the pontine tegmentum with ascending aminergic projections to the forebrain in 12 cases of frontotemporal dementia (FTD). The nuclear grays examined were the nucleus centralis superior (NCS), a part of the nucleus raphae dorsalis (NRD), and the locus coeruleus (LC). The results were compared with 30 cases of Alzheimer's disease (AD) and 35 non-demented controls. In addition to the graph evaluations, neuronal cytoplasmic inclusion bodies were stained by silver impregnation and ubiquitin (Ub) and tau immunohistochemistry. The FTD cases showed a significant, 40%, decline in number of neurons in the NCS and NRD, while the LC was spared. The magnitude of neuronal loss matched that of AD where, by contrast, the LC was also severely changed. Amyloid deposition and Alzheimer neurofibrillary tangles occurred in the aminergic nuclei almost exclusively in AD and, to a minor extent, in some aged controls. No cytoplasmic inclusion bodies were found in the aminergic nuclei of the FTD cases. However, 6 cases had Ub-positive but tau-negative neuronal inclusions in the hippocampal dentate fascia and in layer 2 of the prefrontal isocortex, and 3 showed clinical and histological signs of motor neuron disease. Our results suggest that the serotoninergic raphe nuclei with ascending projections to the forebrain, but not the LC, become directly or indirectly involved in frontotemporal dementia both with and without motor neuron disease.
Asunto(s)
Demencia/patología , Lóbulo Frontal/patología , Vías Nerviosas/patología , Neuronas/patología , Puente/patología , Serotonina/metabolismo , Lóbulo Temporal/patología , Adulto , Anciano , Anciano de 80 o más Años , Péptidos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Antígenos CD/metabolismo , Antígenos de Diferenciación Mielomonocítica/metabolismo , Demencia/metabolismo , Demencia/fisiopatología , Giro Dentado/metabolismo , Giro Dentado/patología , Giro Dentado/fisiopatología , Femenino , Lóbulo Frontal/metabolismo , Lóbulo Frontal/fisiopatología , Proteína Ácida Fibrilar de la Glía/metabolismo , Humanos , Inmunohistoquímica , Locus Coeruleus/metabolismo , Locus Coeruleus/patología , Locus Coeruleus/fisiopatología , Masculino , Persona de Mediana Edad , Vías Nerviosas/metabolismo , Vías Nerviosas/fisiopatología , Neuronas/metabolismo , Norepinefrina/metabolismo , Puente/metabolismo , Puente/fisiopatología , Corteza Prefrontal/metabolismo , Corteza Prefrontal/patología , Corteza Prefrontal/fisiopatología , Núcleos del Rafe/metabolismo , Núcleos del Rafe/patología , Núcleos del Rafe/fisiopatología , Lóbulo Temporal/metabolismo , Lóbulo Temporal/fisiopatología , Ubiquitinas/metabolismo , Proteínas tau/metabolismoRESUMEN
The authors report on a patient who had undergone resection of a left-sided temporal giant cell glioblastoma at the age of 69 years and who survived for more than 17 years. This man had not undergone postoperative radiotherapy or adjuvant chemotherapy. He died at the age of 86 years without clinical evidence of tumor recurrence. Histologically, the lesion was characterized by highly pleomorphic tumor cells (including bizarre multinucleated giant cells) with high mitotic activity, large necroses, and prominent mononuclear infiltration. A point mutation in the TP53 tumor suppressor gene (c.524G>A; R175H) and no epidermal growth factor receptor gene amplification were revealed on molecular genetic analysis. No diagnostic chromosomal imbalances were identified on comparative genomic hybridization, although the average ratio profile for chromosome 10 indicated loss of 10p15 in a subpopulation of tumor cells. This patient is exceptional because tumor resection, probably in conjunction with a marked antitumor immune response, apparently resulted in eradication of the lesion.
Asunto(s)
Neoplasias Encefálicas/fisiopatología , Neoplasias Encefálicas/cirugía , Glioblastoma/fisiopatología , Glioblastoma/cirugía , Lóbulo Temporal , Anciano , Secuencia de Bases/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Genes p53/genética , Glioblastoma/genética , Glioblastoma/patología , Humanos , Inmunohistoquímica , Masculino , Biología Molecular , Hibridación de Ácido Nucleico , Mutación Puntual/genética , Factores de TiempoRESUMEN
The twin-reversed arterial perfusion (TRAP) sequence, or acardia, is the most severe complication in monozygotic twinning. Although more than 400 cases with TRAP sequence were reported since 1533, thorough investigations of the brain in those cases with a rudimentary head remained infrequent. We report a TRAP sequence with microcephaly and a severely rudimentary brain anlage. Neuropathologic examination clearly demonstrated two types of change: (1) developmental arrest of brain at the prosencephalic stage (holoprosencephaly), and (2) hypoxic damage to the holospheric brain mantle with cystic change (hydranencephaly). With reference to previous studies in experimental animals showing that lack of oxygen during early embryogenesis can induce severe disruptions of head-brain and heart formation, it is concluded that oxygen deficiency due to TRAP may be responsible not only for the encephaloclastic changes in the acardius anceps, but for the developmental arrest of the brain cases as well. This would make it unnecessary to postulate additional primary causes such as asymmetric zygote cleavage (Schwalbe, '07) for the maldevelopment.
Asunto(s)
Anomalías Múltiples/patología , Encéfalo/anomalías , Enfermedades en Gemelos , Corazón Fetal/anomalías , Médula Espinal/anomalías , Autopsia , Encéfalo/patología , Cesárea , Muerte Fetal , Corazón Fetal/patología , Humanos , Recién Nacido , Masculino , Médula Espinal/patología , Gemelos MonocigóticosRESUMEN
Neuroimaging studies of cerebellar atrophy in schizophrenia have yielded contradictory results. In computer-tomography (CT) studies, cerebellar atrophy was found in up to 40% of schizophrenic patients. However, several recent magnetic resonance imaging (MRI) studies could not replicate these early findings; in addition, contradictory observations of enlargement of vermal structures were reported. In contrast to the number of CT and MRI studies, there are only a few neuropathological reports on this subject. In a post-mortem study we analyzed the midsagittal vermal area of formaldehyde-fixed cerebella of 12 deceased schizophrenic patients and 12 age- and gender-matched control subjects by using morphometrical methods. Statistical analysis using ANOVA revealed no significant group effects, but there were interactions with gender and cerebellar brain weight. In view of the present results, the common concept of cerebellar atrophy in schizophrenic patients appears premature. Gender effects and secondary processes (e.g., relevant alcohol or drug abuse) cannot be excluded as possible factors causing decrease of vermal areas in schizophrenic patients.
Asunto(s)
Cerebelo/diagnóstico por imagen , Cerebelo/patología , Esquizofrenia/diagnóstico por imagen , Esquizofrenia/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Atrofia/diagnóstico por imagen , Atrofia/patología , Cerebelo/anomalías , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Cambios Post Mortem , Radiografía , Factores de TiempoRESUMEN
Two cases out of a sample of 41 fetuses and infants with prosencephalic malformation, observed at the Institute of Pathology and Department of Neuropathology of the University of Heidelberg, are described here in detail. These cases presented grossly with microcephaly and missing forebrain, appearing to be cases of aprosencephaly. However, in one of these cases glio-mesenchymal membranes with an ependymal outline, consistent with the microscopic appearance of the dorsal sac membrane in holoprosencephaly and obviously representing remnants of a collapsed primitive prosencephalic vesicle, could be demonstrated. In the other case only hindbrain structures, with the exception of the cerebellum, were present without any demonstrable remnants of a prosencephalon. We propose that the microscopic specification of a primitive prosencephalic vesicle in the first case and similar cases does not justify the diagnosis of atelencephaly/aprosencephaly because the prosencephalon was not really missing (pseudo-aprosencephaly). The prosencephalic anlage had been formed but remained vesicular without further differentiation of a holospheric brain mantle as in common holoprosencephaly ('vesicular forebrain'). We believe that pseudo-aprosencephaly represents the most primitive form of holoprosencephaly, in which the forebrain remains as a complete sac, linking classical holoprosencephaly with 'true' aprosencephaly, i.e., defective prosencephalic anlage due to developmental arrest. The 'vesicular forebrain' allows one to extend the classification of Probst by an additional category which might be termed complete sac category, intercalated between the dorsal sac category and 'true' atelencephaly/aprosencephaly.
Asunto(s)
Anencefalia/patología , Prosencéfalo/anomalías , Femenino , Feto , Humanos , Recién Nacido , Masculino , Embarazo , Prosencéfalo/patologíaRESUMEN
An in vivo bromodeoxyuridine (BrdU) labeling index (LI) was estimated in 43 cases of astrocytic tumors and mixed gliomas by one hour intra-operative intravenous infusion at a dose of 200 mg/m2 and correlated with (a) histological grading using a computer aided malignancy classifier TESTAST-268; and (b) histological typing using WHO classification. The lowest BrdU LI was seen in pilocytic and gemistocytic astrocytomas followed by astrocytomas, anaplastic astrocytomas and glioblastoma multiforme in that order. Mixed oligoastrocytomas followed the pattern of their astrocytic counterparts. Tumors of similar histological type showed different BrdU LI values especially amongst astrocytomas and glioblastomas. A statistically significant difference in the BrdU LI was also noted between the higher TESTAST grades of astrocytomas (T III and IV) versus the lower TESTAST grades (T II). Unlike earlier reports in literature, in the present study the category of BrdU LI of <1 contained no case of anaplastic astrocytoma or glioblastoma multiforme (TESTAST grades III and IV). Likewise, the category of BrdU LI >5 contained only anaplastic astrocytoma and glioblastoma multiforme (TESTAST grades III and IV). Maximum spread of cases was seen in the BrdU LI category of 1-5, not only in terms of histological types but also TESTAST grades. Thus there appeared to be a positive trend of increasing BrdU LI values both with histological types and increasing TESTAST grades. Further, an interesting observation was that by using a combination of TESTAST grades and BrdU LI, the histologically homogenous glioblastoma group could be further subdivided into 4 categories which showed a trend towards prognostic correlation. Thus, this study though preliminary with number of cases being small in some groups, highlights the possible usefulness of combined histological typing, TESTAST grading and in vivo BrdU LI for prognostication of gliomas especially glioblastoma multiforme.
Asunto(s)
Astrocitoma/diagnóstico , Neoplasias Encefálicas/diagnóstico , Bromodesoxiuridina , Diagnóstico por Computador/métodos , Glioma/diagnóstico , Astrocitoma/clasificación , Astrocitoma/mortalidad , Astrocitoma/patología , Neoplasias Encefálicas/clasificación , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/patología , Femenino , Glioma/clasificación , Glioma/mortalidad , Glioma/patología , Humanos , Masculino , Estadificación de Neoplasias , Pronóstico , Organización Mundial de la SaludRESUMEN
A graph method was employed to analyse spatial neuronal patterns of pontine nuclei with ascending aminergic projections to the forebrain (nucleus centralis superior (NCS), raphes dorsalis (NRD) and locus coeruleus (LC)), in Alzheimer disease (AD), Huntington disease (HD), and vascular (VD) as well as "mixed-type" (VA) dementia, compared with non-demented controls (CO) and a small sample of brains from schizophrenics ("dementia praecox" (DP)). The quantitative evaluations by the "minimal spanning tree (MST)" were complemented by rough neurofibrillary tangle (NFT) counts and by semiquantitative immunohistochemical assessment of amyloid deposition, neuritic plaque formation, and cellular gliosis. The AD cases showed a significant decline of neuronal density in all nuclei examined, as compared with controls and DP. Neuronal loss was not significant in VD, while the mixed cases with both vascular and Alzheimer-type pathology exhibited pronounced changes of neuronal density. Amyloid deposition occurred almost exclusively in AD and VA, as a rule, being of moderate degree, except for two presenile AD cases where it was marked. NFT were significantly increased in all nuclei in AD and in the VA cases, while they only occasionally appeared beyond age 55 in HD, DP and CO. The four HD cases showed in the NCS and NRD neuronal loss as severe as in AD. This neuronal loss implicates impairment of serotoninergic and noradrenergic neuromodulation as one basic mechanism promoting dementia in AD, VA and perhaps in HD.
Asunto(s)
Tronco Encefálico/patología , Núcleo Celular/ultraestructura , Demencia Vascular/patología , Demencia/patología , Enfermedades Neurodegenerativas/patología , Neuronas/patología , Prosencéfalo/patología , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/patología , Tronco Encefálico/anatomía & histología , Tronco Encefálico/citología , Estudios de Casos y Controles , Núcleo Celular/patología , Femenino , Humanos , Enfermedad de Huntington/patología , Procesamiento de Imagen Asistido por Computador , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Neuronas/citología , Prosencéfalo/citología , Esquizofrenia/patologíaRESUMEN
We report a patient who developed stiff-man syndrome, including disabling shoulder subluxation and wrist ankylosis, in association with breast cancer. Immunologic investigations disclosed autoimmunity directed against not only glutamic acid decarboxylase but also amphiphysin, a 128-kd protein located in the presynaptic compartment of neurons. The patient improved after surgery and corticosteroid treatment and has been stable for nearly 4 years on only anti-estrogenics. The triad of stiff-man syndrome, breast cancer, and autoantibodies against amphiphysin identifies a new autoimmune paraneoplastic syndrome of the CNS.
Asunto(s)
Neoplasias de la Mama/complicaciones , Carcinoma Ductal de Mama/complicaciones , Síndromes Paraneoplásicos/complicaciones , Síndrome de la Persona Rígida/etiología , Animales , Autoanticuerpos/sangre , Autoanticuerpos/aislamiento & purificación , Western Blotting , Diagnóstico Diferencial , Femenino , Glutamato Descarboxilasa/inmunología , Humanos , Técnicas para Inmunoenzimas , Persona de Mediana Edad , Proteínas del Tejido Nervioso/inmunología , Síndromes Paraneoplásicos/inmunología , Pruebas de Precipitina , Ratas , Síndrome de la Persona Rígida/diagnóstico , Síndrome de la Persona Rígida/inmunologíaRESUMEN
Agenesis of the cerebellar vermis (paleocerebellar agenesis) with fusion of the cerebellar hemispheres (rhombencephalosynapsis) is a rare malformation of the central nervous system (CNS). Its combination with synencephaly (telencephalosynapsis), telencephalic ventricular aplasia, aqueductal atresia and cystic fourth ventricle has not yet been described, as far as we know. Here, we report this combination in a 23-weeks' gestation male fetus who was aborted to a 24-year-old diabetic mother. In this fetus with cerebral and cerebellar hemispheric fusion, vermian agenesis was associated with a Dandy-Walker-like posterior fossa cyst, in spite of the fusion of the hypoplastic cerebellar hemispheres. The CNS malformations were further accompanied by dysmorphic facial stigmata such as unilateral atresia of the external ear, ocular hypertelorism and a broad nasal bridge. Preaxial polydactyly and contractures of the upper limbs were the only associated non-cranial abnormalities. Cytogenetic studies revealed a numerically and structurally normal male (46, XY). The malformation complex described in this fetus of a mother with antedating pregnancy diabetes appears to represent a previously undescribed aberrant syngenetic CNS phenotype, some basic teratogenetic aspects of which will be discussed in this paper.
Asunto(s)
Ventrículos Cerebrales/anomalías , Fosa Craneal Posterior/anomalías , Síndrome de Dandy-Walker/patología , Rombencéfalo/anomalías , Telencéfalo/anomalías , Adulto , Ventrículos Cerebrales/patología , Fosa Craneal Posterior/patología , Femenino , Humanos , Masculino , Embarazo , Rombencéfalo/patología , Telencéfalo/patologíaRESUMEN
This article aims at drawing attention to the peculiar association of intense exposure to sunlight and subacute development of sensory neuropathy which was seen in 7 psychiatric patients treated with the phenothiazine derivative, perazine. Three patients additionally developed bilateral VII nerve palsy. Symptoms followed a monophasic course with almost complete remission. Routine neurophysiology suggested axonal neuropathy confirmed by sural nerve biopsy in 1 patient. A toxic origin of neuropathy is supposed, possibly induced by phenothiazine photoproducts, which may cause cell damage via lipid peroxidation.
Asunto(s)
Helioterapia , Neuritis/inducido químicamente , Neuritis/etiología , Perazina/efectos adversos , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/etiología , Traumatismos por Radiación , Adulto , Anciano , Enfermedad Crónica , Parálisis Facial/inducido químicamente , Parálisis Facial/etiología , Femenino , Humanos , Masculino , Conducción Nerviosa , Neuritis/patología , Perazina/uso terapéutico , Enfermedades del Sistema Nervioso Periférico/patología , Esquizofrenia/tratamiento farmacológico , Nervio Sural/patología , Nervio Sural/fisiopatologíaRESUMEN
Forty three cases of astrocytic tumors and mixed gliomas were studied with the aim of evaluating the reproducibility of the Kernohan grading system vis a vis (a) grading using computer-aided malignancy classifier TESTAST 268 and (b) grading by quantitative morphometric evaluation of the various histological parameters of TESTAST 268. These patients were then followed up for variable periods with a maximum of forty months. High inter and intra-observer variability were observed in the Kernohan grading system. TESTAST 268 was found to be simpler, rapid and more reproducible. However, one drawback observed of this system was that it did not completely eliminate inter-observer variability because there was still some subjectivity in assignment of the categorical values against the histological features. Morphometric evaluation of the semi-quantitative assignment values of the 4 histological variables in the TESTAST 268 classifier using Zeiss Morphomat-30 revealed a statistically significant difference between the clusters of the measured quantitative values. A repeat grading using TESTAST 268 and categorical assignment values of histological features derived from the absolute values obtained by morphometry resulted in complete elimination of inter-observer variability. Thus, this study highlights the importance of objectivisation using TESTAST 268 and histologic morphometry in the grading of gliomas. However, since this is a preliminary study on a small number of cases, no cut off values of these measurements have been proposed.
Asunto(s)
Astrocitoma/patología , Neoplasias Encefálicas/patología , Diagnóstico por Computador , Glioma/patología , Adolescente , Adulto , Anciano , Astrocitoma/clasificación , Astrocitoma/mortalidad , Neoplasias Encefálicas/clasificación , Neoplasias Encefálicas/mortalidad , División Celular/fisiología , Niño , Preescolar , Endotelio Vascular/patología , Estudios de Evaluación como Asunto , Femenino , Glioma/clasificación , Glioma/mortalidad , Humanos , Masculino , Mitosis/fisiología , Necrosis , Neovascularización Patológica , Variaciones Dependientes del Observador , Reproducibilidad de los Resultados , Programas Informáticos , Tasa de SupervivenciaRESUMEN
The human entorhinal region consists of a number of areas; however, there is no generally accepted nomenclature for these cytoarchitectonic fields, and the designation of its constituent layers or strata is a matter of controversy. Here, we consider a hitherto neglected adjacent field, the preamygdaloid claustrocortex. Its medial subfield has a small common border with the rostromedial entorhinal region (width maximal 2 mm). Both fields are cytoarchitectonically rather similar. The rostromedial oral entorhinal field lacks ascending terminal islands. Its unusually small pre-alpha cells are arranged in a thin band or small clusters consisting of pyramidal, triangular, or polymorphic cells. The conspicuous chromophilic pre-beta cell clusters are composed of a variety of cell types, including groups of 'immature' spindle-shaped or bipolar nerve cells. Furthermore, a rare sulcus within the entorhinal region (central sulcus of the entorhinal region: observed in 4% of the 450 brains examined) is associated with an unusual lamination of the entorhinal layers in its wall and floor. Both the specific shape and arrangement of neurones in the claustrocortical-rostral entorhinal border region and the unusual lamination within the rare central entorhinal sulcus are regarded as reflecting neurodevelopmental disturbances characteristic of schizophrenic brains. In contrast, our observations in a large sample of serially sectioned brains from controls, schizophrenics, and patients suffering from neuropsychiatric diseases other than schizophrenia do not support this assumption.
Asunto(s)
Corteza Entorrinal/anatomía & histología , Trastornos Mentales/diagnóstico , Enfermedades del Sistema Nervioso/diagnóstico , Adulto , Anciano , Giro Dentado/patología , Corteza Entorrinal/patología , Femenino , Variación Genética , Humanos , Sistema Límbico/patología , Masculino , Trastornos Mentales/patología , Persona de Mediana Edad , Enfermedades del Sistema Nervioso/patología , Neuronas/patologíaRESUMEN
The formation of beta A4 amyloid protein in neuritic plaques in Alzheimer's disease (AD) and advanced age is a complex process that involves a number of both cellular and molecular mechanisms, the interrelations of which are not yet completely understood. We have examined quantitatively, in AD and aged controls an extended spectrum of amyloid plaque-related cellular and molecular factors and the cortical synaptophysin immunoreactivity (synaptic density) in order to check for interrelations between them by multifactorial analysis. In 3 cases of senile dementia of the Alzheimer type (SDAT) aged 72, 80 and 82 years, and 9 controls aged 43-88 (mean age 65) years, the cortical synaptophysin immunoreactivity was assessed, together with the numbers of neurons, astrocytes and microglial cells, senile plaques, of tangle-bearing neurons, and the amount of beta A4 amyloid precursor protein (APP) with and without the Kunitz type serine protease inhibitor (KPI) domain. The main results were: APP including the KPI domain (KPI-APP) correlated with the number of neuritic plaques, regardless of whether they occurred in SDAT or non-demented controls. There was no significant difference in the amount of KPI-APP between SDAT and controls. Conversely, APP695 (without KPI) was significantly reduced in SDAT. KPI-APP did not correlate with the synaptophysin immunoreactivity (RGVA), while APP695 showed a significant correlation with the latter in all evaluations. It also correlated with the neuron counts, which was not true for KPI-APP. These results support previous findings indicating that KPI-APP is an important local factor for amyloid deposition in the neuritic plaques, both in AD and in non-demented aged people. On the contrary, KPI-APP does not seem to be significantly involved in the mechanisms of synaptic change outside of the plaques.
Asunto(s)
Enfermedad de Alzheimer/metabolismo , Precursor de Proteína beta-Amiloide/análisis , Proteínas del Tejido Nervioso/análisis , Neuritas/patología , Péptidos , Proteínas de Plantas , Sinaptofisina/análisis , Inhibidores de Tripsina/análisis , Adulto , Anciano , Anciano de 80 o más Años , Envejecimiento/metabolismo , Envejecimiento/patología , Estudios de Casos y Controles , Causalidad , Humanos , Persona de Mediana Edad , Estructura Terciaria de ProteínaRESUMEN
We report six cases of presenile (five) and senile (one) progressive dementia with a mild-to-marked frontal or frontotemporal atrophy and ventricular dilation (Frontal Lobe Degeneration [FLD]). The most prominent microscopic features were layer-dependent neuronal depletion of the cortex, spongiosis, and cortical and subcortical gliosis. Five cases showed additional degeneration of the S. nigra, and two also had motor neuron disease. Despite the absence of Pick cells and bodies, such cases have many features in common with Pick atrophy. Because Pick cells and bodies are inconstantly occurring features in otherwise typical cases of Pick atrophy, they cannot be regarded as inevitable markers of the latter. In our opinion, cases with mild frontal or frontotemporal atrophy as described herein and by others match the grades 1 and 2 in terms of Schneider's classification of Pick atrophy [37]. As long as the etiology of both Pick atrophy and the so-called FLD is unknown, and we finally have to follow morphological criteria for classification, there is apparently no convincing reason to introduce a separate category, such as FLD or FTA, for the cases with moderate or mild frontal atrophy and dementia of frontal lobe type, which can be sufficiently classified with the Pick spectrum of lobar atrophy.
Asunto(s)
Demencia/diagnóstico , Demencia/fisiopatología , Lóbulo Frontal/fisiopatología , Degeneración Nerviosa , Adulto , Anciano , Demencia/psicología , Diagnóstico Diferencial , Femenino , Lóbulo Frontal/ultraestructura , Humanos , Masculino , Persona de Mediana Edad , Psicometría , Índice de Severidad de la Enfermedad , Escalas de WechslerRESUMEN
We report the cases of a 70-year old man with left temporal brain atrophy and of a 39-year-old man with neuropathologically verified frontal lobe degeneration (FLD) of Non-Alzheimer type. 10 patients with FLD collected during a prospective study on degenerative dementia had more severe volumetric brain changes and less severe quantitative band power changes than a group of matched patients with clinically diagnosed Alzheimer's disease.
Asunto(s)
Enfermedad de Alzheimer/diagnóstico , Demencia/diagnóstico , Lóbulo Frontal/patología , Lóbulo Temporal/patología , Adulto , Anciano , Enfermedad de Alzheimer/fisiopatología , Atrofia , Demencia/fisiopatología , Diagnóstico Diferencial , Electroencefalografía , Lóbulo Frontal/fisiopatología , Humanos , Masculino , Degeneración Nerviosa/fisiología , Pruebas Neuropsicológicas , Lóbulo Temporal/fisiopatología , Tomografía Computarizada por Rayos XRESUMEN
A female child of healthy parents developed rotary nystagmus at the age of 15 months. Ophthalmoscopy disclosed incomplete optic atrophy. Blood tests, EEG and CT scans were normal. At 20 months progressive muscular weakness and wasting with limb-girdle distribution commenced, followed later by disturbance of gait. From muscle and nerve biopsy the diagnosis of a peripheral neuropathy with neurogenic muscular atrophy was made. No mental change occurred. At 23 months she sustained cardiac arrest and was resuscitated; thereafter, she remained in a vegetative state and expired 9 months later. Her brain was markedly atrophic and firm. Diffuse old ischemic necroses and neuronal loss with gliosis were found in the cortex, the neostriatum, the thalamus, parts of the lower brainstem, and the cerebellum. Her optic nerves and tracts showed complete atrophy. The spinal cord exhibited degeneration and loss of motor neurons with cervical accentuation. The intermediolateral nuclei, the dorsal nuclei and the spinal ganglia were also involved. There was demyelination of the posterior funiculi, the pyramidal tracts, and the sciatic, peroneal, sural, and superior frontal nerve. The voluntary muscles exhibited large group atrophy with liposclerotic change and limb-girdle predominance. The neck, tongue and ocular muscles were also involved, as were, to a less extent, the lower limbs. Although the loss of motor neurons in the spinal cord and at the bulbar level with the typical pattern of neurogenic muscular atrophy, as well as its distribution, resemble the facioscapulo-humoral type of heredity motor neuropathy (HMN), early onset, rapid course, sensory and autonomic involvement, and atrophy of the optic nerve do not fit this or any one type of HMN.
Asunto(s)
Enfermedades del Sistema Nervioso Autónomo/patología , Oftalmopatías/patología , Atrofias Musculares Espinales de la Infancia/patología , Atrofia/patología , Encéfalo/patología , Femenino , Ganglios Espinales/patología , Ganglios Espinales/fisiopatología , Humanos , Lactante , Músculos/patología , Miocardio/patología , Neuronas Aferentes/fisiología , SíndromeRESUMEN
It has been shown recently that in Alzheimer's disease the degree of dementia is strongly correlated with a reduction of the synaptophysin reactivity of the cortical neuropil as a measure of synapse density, while counts of neuritic plaques showed a weak correlation. This suggests that mechanisms acting at the synaptic level, finally resulting in a numerical decline of synapses, may represent an important factor in the pathogenesis of dementia. Under these aspects, we wanted to examine whether changes of synaptophysin immunoreactivity may also occur in dementia of vascular origin such as Binswanger's disease, where the white matter atrophy is usually conceived to be the main morphologic correlate of dementia. However, infrequently patients with morphologically typical Binswanger's subcortical encephalopathy including white matter atrophy are not demented. We found in 9 cases of vascular dementia of Binswanger type a significant reduction in synaptophysin immunoreactivity of the cortical neuropil (9.1%), the magnitude of which was not much less than in Alzheimer type dementia (10.9%). These results suggest that a reduction in cortical synaptic population density may also play a significant role in the pathogenesis of dementia in Binswanger's disease. In view of the fact that similar conditions have been shown to occur in neurodegenerative disorders with dementia other than Alzheimer type dementia, there seems to be evidence for a possible common pathogenetic link between these forms of dementia at the synaptic level, where different etiologic factors may result in similar changes.
Asunto(s)
Enfermedad de Alzheimer/metabolismo , Corteza Cerebral/metabolismo , Demencia Vascular/metabolismo , Red Nerviosa/metabolismo , Sinaptofisina/metabolismo , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Valores de ReferenciaRESUMEN
After the introduction of 4-methylumbelliferyl-2-acetamido-2-deoxy-beta A-D-glucopyranoside (4MUG) and its sulfated form (4MUGS) in the pre- and postnatal diagnosis and carrier identification of gangliosidosis genotypes, infrequent forms of the GM2 gangliosidosis Type B (Tay-Sachs disease) have been observed which show normal activity of Hexosaminidase A (Hex A) isoenzyme with the substrate 4MUG but absent or deficient activity against the sulfated form 4MUGS. Here we report the observation of a German/Hungarian boy aged 12 when he died with a prolonged course of a neurodegenerative disorder, later biochemically identified as a GM2 gangliosidosis B1-variant which is characterized by a deficient Hex A activity only against 4MUGS. The first clinical symptoms had occurred after the age of 14 months with a clear manifestation of the disease at age 3, when he presented disturbances of movement and tended to fall down. The slowly progressive course with brain atrophy, seizures and severe mental deterioration resulted in death after almost 9 years. At autopsy, the typical light microscopic neuronal changes of a "lysosomal storage disorder" were found, with multilamellar concentric bodies (MCB) and Zebra bodies in the neuronal cytoplasm at the electron microscopic level.