Vascular fibrosis and calcification in the hippocampus in aging, Alzheimer disease, and Down syndrome.

Study of the hippocampal formation of 82 subjects, including 25 control subjects from 33 to 83 years of age, 34 subjects with Alzheimer disease (AD) from 65 to 89 years of age, and 23 subjects with Down syndrome (DS) from 33 to 72 years of age, revealed hippocampal vasculopathy with fibrosis and calcification (VFC) in 40% of control, 59% of AD, and 4% of DS subjects. VFC starts in the precapillaries/capillaries in the molecular layer of the dentate gyrus (DG) and expands to the granule cell and polymorphic cell layer of the DG, and to the stratum lacunosum/molecular in the CA1 sector. Vasculopathy spreads from the tail to the body and, in a few cases, to the head of the hippocampal formation. Light and electron microscopy reveal thickening of the vascular wall with fibrosis, calcification, and enforcement of the astrocyte interface with vessels with anchorage densities associated with hemidesmosome-like structures. In moderately and severely affected cases, fragmentation and removal of calcified and occluded vessels result in local reduction of vascular network. In two AD subjects, severe vascular calcification extending from the tail to the head of the hippocampal formation was associated with loss of almost all neurons in the CA1 sector and in the subiculum proper, corresponding to hippocampal sclerosis. The topography of affected vessels and the patterns of neuronal loss reflect the middle hippocampal artery distribution with its precapillary/capillary network. The similar prevalence of vasculopathy in the AD group and in the age-matched control group, and the presence of hippocampal VFC in only one subject in the DS cohort, 96% of which is affected by Alzheimer-type pathology, oppose the link between AD and this form of vasculopathy. However, severe VFC affects the pattern of AD pathology locally by deletion of neurofibrillary degeneration and beta-amyloidosis in the CA1 sector, subiculum proper, and the molecular layer of the dentate gyrus. Hippocampal VFC appears to be a form of vascular pathology with a unique predilection for the middle hippocampal artery and corresponding capillary network, which results in patchy neuronal loss in moderately affected subjects and in almost total neuronal loss in the area of impaired blood supply in severely affected subjects. These observations suggest an etiologic link between hippocampal VFC and hippocampal sclerosis.

Neuronal loss and beta-amyloid removal in the amygdala of people with Down syndrome.

The decrease in the number of neurons free of neurofibrillary changes, neurons with neurofibrillary degeneration, and the total volume of beta-amyloid (A beta) deposits in the amygdala of people with Down syndrome and in late stages of Alzheimer disease were estimated by using morphometry and regression analysis. This model predicts that the duration of neurofibrillary changes from the pretangle stage to ghost tangles is approximately 4.7 years. The correlation between the decrease in the number of neurons and the decrease in the amount of A beta indicates that amyloid deposition is associated with neurons and that loss of neurons causes decrease in A beta deposition. The presence of neurons only with neurofibrillary tangles, and the absence of the amyloid deposits predicted by regression analysis suggest that neurons with tangles are not engaged in amyloid deposition. The disappearance of amyloid by approximately 2.2 years after loss of neurons free of neurofibrillary changes indicates that A beta deposits are degradable and removable and that even in severely atrophic amygdala, there are mechanisms of amyloid resolution. This study shows that in normal aging in the amygdala, extracellular A beta appears later than neurofibrillary changes.

Cell-type-specific enhancement of amyloid-beta deposition in a novel presenilin-1 mutation (P117L).

The presenilin-1 (PS1) gene mutation (Pro117Leu), recently identified in a Polish family is characterized by the earliest reported onset (from 24-31 years) of Alzheimer disease (AD) and a very short duration of disease (4-6 years). The neuropathology of 2 subjects with this PS1 mutation (ages at death: 35 and 37 years) was compared to four Down syndrome (DS) patients (mean age at death: 62 years) and 4 sporadic AD patients (mean age at death: 79 years with a mean duration of disease of 18 years). The Polish familial AD (FAD) patients showed a marked increase in the amyloid burden of 2 6-fold in most areas of the brain. The entorhinal cortex was an exception where the amyloid burden was similar in each category of patient. Some brain regions of the Polish FAD patients showed a massive increase of amyloid, such as the molecular layer of the cerebellum where a 7- and 25-fold increase was noted, compared with DS and sporadic AD patients respectively. The cerebellar vessel amyloid burden was also greatly increased in the FAD patients, reflecting a vascular compartment specific increase of amyloid beta deposition. The presence of this PS1 mutation has an even greater effect on both vascular and parenchymal amyloid deposition, than the overexpression of the amyloid beta precursor protein present in DS patients, suggesting that PS mutations can be a critical factor determining amyloid deposition.

Embryonal carcinoma of the pineal gland with yolk sac tumor differentiation. A case report.

Twenty three old male patient was diagnosed as a pineal gland tumor and was operated in neurosurgical ward. He died four weeks later due to pneumonia and respiratory failure. Clinical diagnosis was based on computer tomography (CT) and magnetic resonance image (MRI) examination. Histological study of a biopsy and autopsy specimens showed embryonal carcinoma with yolk sac tumor differentiation. The diagnosis was supported by positive cytokeratin, placental alkaline phosphate and alpha-fetoprotein immunostainings.

[A case of fatal hemolytic-uremic syndrome with central nervous system manifestations]. / Przypadek zespolu hemolityczno-mocznicowego ze zmianami w ukladzie nerwowym.

Twelve years old girl who died from haemolytic uraemic syndrome (hus) on post mortem neuropathological examination showed cerebral purpura and demyelination focus with glial-mesenchymal reaction. The problem with factor is responsible for cerebral lesions, direct allergic reaction causing hus or uraemia in consequence of acute renal failure but also activating allergic processes, is discussed.

Migration disorders leading to a wide spectrum of brain malformations in a case with multiorganic dysgeneses: A new syndrome?

A case of a preterm infant who died with multiorgan, mainly cerebro-oculo-cutaneous malformations is presented. The brain dysgenesias consist of early disturbances of neuronal migration. They result on appearance of nodular subcortical heterotopias, cortical anomalies including pachy- and polymicrogyria and focal intrusion of numerous abnormally migrating nerve cells into leptomeninges. A various degree of nerve and glial cell maturity was observed within heterotopic tissue. The other malformations include eye, skin and internal organs anomalies. Similarities and differences between our case and another previously described cases were discussed but it seems difficult to include the analysed case into one of the known syndromes.

Different developmental rates of selected brain structures in humans.

Various rates of development are characteristic for particular structures of the human central nervous system (CNS). The differences of the maturing brain stem and telencephalon are evident in a routine neuropathological examination. The fetal and postnatal archi- and neocortex also reveals uneven levels of maturation. In order to precisely describe those differences in humans we performed a morphological and morphometric study on the dorsal vagal nucleus of the medulla oblongata, on Ammon's horn and on neocortex from midgestation to the 18th postnatal month. The numerical density of neurones, cell perikarya and nuclear cross-sectional area, and the ratio of nucleus to perikaryon area were measured. The results demonstrate a development-dependent decrease in cell density and progressive differentiation of neurones according to their changing size. They express a process of maturation which differs in rate across the CNS structures examined.

Meningiomas and gliomas in juxtaposition: casual or causal coexistence? Report of two cases.

Two cases of meningioma and glioma established in biopsy material from one or more than one operation are reported. In these cases, an originally benign meningioma was followed by the development of anaplastic astrocytoma in close juxtaposition to the site of first operation. The close juxtaposition of two histologically different tumors suggested that one of them might lead to local proliferation and independent growth of the other.

Neurofibromatosis type 2. Case report.

A case of a 24-year-old woman with peripheral paresis of the facial nerve, balance disturbance, hearing loss and epileptic seizures for many years is presented. At time of admission to hospital cerebral magnetic resonance imaging (MRI) showed several large tumors situated supra- and infratentorially. Histological examination of the operated tumors revealed bilateral acoustic schwannomas in the cerebellopontine angles and mixed meningioma in the others. The patient was diagnosed as neurofibromatosis type 2 (NF2) according to clinical criteria for neurofibromatoses. Several months after the last operation, she exhibited weakness of all extremities. On spinal MRI an intramedullary tumor in the cervical region and additional focal lesions along central canal were found. Surgical therapy was not performed because of clinical improvement after dexamethasone treatment and location of lesion in cervical medulla. Our case confirms frequently occurring lack of neurocutaneous changes and late appearance of significant neurological symptoms in NF2.

Vascular malformations associated with other congenital anomalies of the central nervous system: coexistence and possible causal relations.

Two cases of vascular malformations coexisting with other congenital defects of the central nervous system (CNS) are presented here. The first patient was a 14-year-old girl mentally retarded who demonstrated seizures and balance disturbances with onset in early infancy. The neuropathological examination revealed vascular malformations in the pons, diastematomyelia (triple central canal) in the sacral spinal cord and palleocerebellar granular layer dysplasia. The second patient was a 10-year-old boy hospitalized because of purulent dermatitis who suddenly developed recurrent generalized and focal motor seizures. The neuropathological examination disclosed multiple capillary teleangiectases with focal anomalies within cerebral cortex of the frontal and parietal lobes. The relations between several developmental anomalies in the CNS and possible causal relation between such malformations are discussed.

[A case of coexistence of meningioma with intracranial aneurysm in a patient with ruptured aortal aneurysm]. / Przypadek wspólistnienia oponiaka i tetniaka sródczaszkowego u osoby z peknietym tetniakiem aorty.

Fifty-three-year-old woman was admitted to hospital with tetraplegia symptoms and died two hours later. Clinical diagnosis was: cerebral stroke, hypertension in anamnesis. Postmortem examination showed ruptured dissecting aneurysm of thoracic and abdominal segment of aorta, meningioma of right pontocerebellar angle and saccular aneurysm of left inferior, posterior cerebellar artery. The diagnostic difficulties and hypotheses of formation of multifocal of different changes are discussed.

Reaction of microglial cells in human astrocytomas (preliminary report).

Forty human primary brain tumors: twelve protoplasmic, six gemistocytic, four fibrillary and ten anaplastic astrocytomas, eight glioblastomas were submitted for immunohistochemical and histochemical characterization of microglia in tumor tissue and in its surroundings. The following antibodies were used: GFAP, ferritin, CD45RO and lectin RCA-1. It was found that the greatest number of ramified microglia occurred in gemistocytic astrocytomas. In the protoplasmic and fibrillary astrocytomas both the ramified and amoeboid microglia were observed. In glioblastomas and anaplastic astrocytomas the greatest number of amoeboid microglia and very rarely ramified microglial cells were found. It is suggested that differences between the various kinds of astrocytomas determine the difference in the type of microglia reaction. It is assumed that this might be caused by the differences in secreting some factors by these tumors astrocytes.

Microcystic meningioma--a rarely occurring morphological variant of meningioma.

Two cases of microcystic meningioma are reported. They were found by retrospective study of 124 human intracranial meningiomas. Both of the examined tumors were characterized histologically by a great number of cysts of various size intermixed with nests of neoplastic tissue of meningothelial meningioma type. Nevertheless, there were two kinds of cystic changes in these tumors. In the first case, numerous microcysts within the tumor were surrounded by stellate-shaped processes of meningioma's cells. The microcystic space were empty or rarely contained eosinophilic material. The latter tumor demonstrated small agglomerations of microcysts and many macrocystic changes, some of them filled with eosinophilic, PAS and mucicarmine negative material. Additionally, in focal areas of the tumor, single mitotic figures and giant cells with hyperchromasia were present. The authors discuss morphologic variability of the examined tumors and its possible clinical consequences. The pathogenesis of microcystic changes in meningioma is discussed with a brief review of the literature.

Neuropathological variants of cystic encephalopathy in infants.

The aim of our study was to present six cases with cystic changes within the white matter in infant brains and discuss the variants of this type of neuropathological lesions of the developing brain. Two of them exhibited the changes characteristic for cystic leucoencephalopathy. To the others with moderate involvement of gray structures, the term multicystic encephalopathy seems to be more appropriate. The clinical course and the neuropathological features of changes allow to consider them as syndromes characteristic for a given period of brain maturation.

Quantitative studies of human newborns' hippocampal pyramidal cells after perinatal hypoxia.

The quantitative histological study was performed on pyramidal cells of human newborn hippocampus in four control brains, three brains of acute hypoxia and three of chronic hypoxia after perinatal asphyxia. The numerical density of pyramidal cells, neuronal perikarya and nuclear cross-sectional area, ratio of nuclear to perikaryon area in sectors CA1 to CA4 were measured from anterior, middle and posterior part of hippocampus. The mean pyramidal cell density in four sectors of controls ranged from approximately 67,000 to 40,000 neurons/mm3. The sectorial cell density gradient was CA1 > CA3 > CA4 > CA2. Pyramidal cells of CA2 sector were much larger (mean +/- SD) (180 +/- 52 microns 2) than other neurons. Immature small cells (72 +/- 18 microns 2) with high nuclear/perikaryon area ratio (66 +/- 8%) predominated in sector CA1. Due to postnatal brain growth these findings differ from those for adults reported so far by others. In comparison with control brains, statistically significant decline of pyramidal cell density was found in hippocampal CA1 and CA4 sectors of acute hypoxia brains. Significant decline of neuronal density in all sectors of hippocampus as well as of nuclear/perikaryon area ratio in CA1 neurons were found in chronic hypoxia brains. The relatively greater neuronal loss was observed in CA1 sector. The results obtained in morphometric analysis showed that neuronal sensitivity of newborn hippocampus to hypoxia was not dependent on the degree of neuronal maturation and was similar to that reported in adults.

Multinucleated giant cells in areas of the brain stem necrosis after cardiac arrest in two infants.

A rare type of cellular reaction in the brain stem of two infants with cardiac arrest encephalopathy is presented. After cardiac arrest both newborns were resuscitated and put on artificial ventilation. Their survival time amounted to 16 and 18 days, respectively, in a deep coma with areflexia. At the postmortem examination a widespread hemispheric necrosis of the gray and white matter was observed as well as symmetrical necrosis of the tegmental part of the brain stem extending from the midbrain up to medulla. Striking proliferation of blood vessels and large number of multinucleated giant cells originating from monocyte/macrophage lineage was found in the areas of the brain stem necrosis. No evidence of inflammatory process was found. It seems that giant cells appeared as local reaction on disintegration of maturing structures.

Cerebral infarcts in newborns and infants with cyanotic cardiac anomalies.

Neuropathological examination of six brains of newborns and infants who died in the course of congenital cyanotic cardiac anomalies showed focal brain lesions. The material included five cases from two weeks to two months of age, and one two-year-old infant. In two of them, the periventricular ischemic infarcts were found, in one multifocal encephalomalacia due to multiple vascular occlusions, and in three the necrotic foci corresponded to the supply of large cerebral arteries. The character and topography of severe brain lesions, particularly within the hemispheric white matter, were clearly influenced by the immaturity of the cerebral structures.

The widespread but silent cerebral mineralization: a case report.

We present a sporadic infantile case of primary cerebral mineralization with unexpected asymptomatic clinical course. An 11 months old boy with negative familial and gestational data developed normally. He died after two days of fever and rapid course of cardiorespiratory failure due to pneumonia. Parathyroid dysfunction and somatic abnormalities were not evident clinically. Neuropathological examination revealed bilateral, diffuse or pericapillary calcifications in the striatum, cerebral and cerebellar cortex, dentate nucleus and brain stem. The mineralizations were less prominent in the cerebral hemispheres than in cerebellum. A diffuse demyelination was seen in the cerebellum where calcifications were numerous. We suggest that the intracerebral calcifications progressed gradually through a disease course and probably started in the cerebellum. We discuss the lack of clinico-pathological correlations and the nosologic position of the observed syndrome.

[Neuropathological analysis of 8 cases of clinically diagnosed Reye syndrome]. / Analiza neuropatologiczna w 8 przypadkach klinicznie rozpoznanego zespolu Reye'a.

Authors discuss the possible etiopathogenesis of Reye syndrome (RS) on the base of eight own cases presented in this paper and others previously described. The febrile infection was observed on the beginning of the disease in all actually analysed cases and was followed by symptoms of acute damage of liver and brain. The central nervous system lesions present the changes increasing with time from brain oedema to the necrosis of nerve tissue. The oedematous changes could be recognized as a principal cause of unconsciousness and even of coma in RS. When the etiology of RS remain unknown the clinico-pathological observations of such cases incline to formulate three questions: Is an genetically conditioned background necessary which facilitate toxic or infectious factors to induce the RS? Is the etiology of RS only genetically conditioned? Is an specific viral infection the cause of RS?

Cerebral ganglioglioma with long history and unusual prominence of the mesenchymal elements. Case report.

A case of cerebral ganglioglioma, a relatively rare and controversial tumor of the central nervous system, is reported. The histological pattern of the tumor consisted of differentiated neuronal cells and glial elements displaying a various extent of cytologic abnormalities. Beside these two typical components for ganglioglioma, an abundance of collagen fibrils and numerous blood vessels were encountered. The long clinical course manifested by temporal epilepsy preceding clinical diagnosis of brain tumor and peculiar histological appearance seem to be of considerable interest.