Midgut epithelium formation in Thermobia domestica (Packard) (Insecta, Zygentoma).

The origin of midgut epithelium may begin either from yolk cells (energids), tips of stomo- and proctodaeum (ectoderm), inner layer (endoderm) or from both kinds of the above mentioned cells. The origin of the midgut epithelium in wingless insects (Apterygota) has still not been determined. In Thermobia domestica the formation of midgut is much delayed, and it completes in the post-embryonic stage, while the stomo- and the proctodaeum are well-developed in the embryonic period. The energids, which remain inside the yolk, start to migrate to its periphery, where they arrange singly close to cell membrane. The yolk mass with the energids at the 14th day of embryogenesis are referred to as the primary midgut. During the first instar larval stage more and more energids migrate to the yolk periphery and the cell membrane starts to form numerous foldings surrounding the groups of energids, which in turn lead to formation of isolated regenerative cell groups. Eventually the cell membrane invaginations reach the center of the yolk mass. Large cells of the primary epithelium, surrounding the newly formed midgut lumen are formed. The cells of the primary epithelium are filled with yolk and are equipped with microvilli pointing to the midgut lumen. As the yolk is being digested, the process of the primary epithelium cells degeneration begins. The cells are getting shorter and start to degenerate. The definitive midgut epithelium is formed from proliferating regenerative cells. It consists of regularly spaced regenerative cell groups as well as the epithelial cells. The ultrastructure of both these cell groups has been described.

Anomalies of cerebral structures in acranial neonates.

Eleven cases of newborns with acrania and macroscopically diagnosed anencephaly were neuropathologically examined. They presented changes in which 1 group corresponded to the diagnosis of aprosencephaly. In the second group, the development of prosencephalic structures was more advanced. The pathomechanism of the observed anomalies was analyzed in relation to data provided by molecular-genetic classification of nervous system malformations, but that did not exclude the influence of eventual extrinsic factors.

Major histocompatibility complex class II (MHC II) expression in the normal and pathological human foetal spinal cord.

The ability of the specific immune response of organisms is determined by the possibility of synthesis, transport and presentation of the major histocompatibility complex class II (MHC II) molecules on the surface of antigen-presenting cells. MHC II molecules are responsible for the binding, transport and presentation of a foreign antigen to helper T lymphocytes. They also stimulate the multiplication of specific B lymphocytes and determine the type of antibodies produced. The expression of MHC II molecules on the cellular surface of the spinal cord in cervical, thoracic, lumbar and sacral regions was studied on 30 normal human foetuses between 11 and 22 weeks of gestation (GW) and 9 foetuses with genetic defects (Down syndrome, mucopolysaccharidosis, mucoviscidosis or Nori's syndrome) between 17 and 22 GW. The immunocytochemical presence of MHC II molecules was found in all regions of the spinal cord in both groups of foetuses, normal and pathological, during the whole interval under study. The molecules were dispersed in the grey and white matter of the spinal cord and located most frequently on the surface of cells, near the central canal and blood vessels. These cells corresponded morphologically and immunocytochemically with amoeboid and ramified microglia. No differences in MHC II expression between the spinal cord regions or between normal foetuses and those with genetic defects were noted. It seems likely that such an early occurrence of MHC II expression in the spinal cord of foetuses with normal development, as well as the absence of abnormalities in this expression in foetuses with genetic defects, may indicate the significant role of these molecules in the immunological protection of the foetus and thus ensuring normal embryogenesis.

Ultrastructural study of mother and daughter muscle changes with mitochondrial encephalomyopathy.

We present the light and electron microscopy examinations of skeletal muscle biopsies from a 36-year-old mother and her 13-year-old daughter with mitochondrial encephalomyopathies. Clinical signs and symptoms suggesting mitochondrial disease, such as disseminated neurological symptoms, visual and hearing disturbances, mental disability, exercise intolerance, heart conduction disturbances, short stature, family history, were present in both patients. The mother's niece (8 years old) also died with progressive neurological disorder. CT showed cerebral and cerebellar atrophy in mother and multifocal subcortical atrophy in daughter. There was lactic acidosis in blood serum and cerebrospinal fluid in daughter. In the daughter's muscle a lot of fibres looked like ragged red fibres. Electron microscopic examination revealed the alterations of mitochondria in skeletal muscle of both patients that concerned the number, size, shape and the fine structural appearance of the mitochondria. The most characteristic mitochondrial abnormalities in daughter's muscles were paracrystalline inclusions in the intracristal space. In mother's muscles most of the mitochondria were markedly enlarged and they possessed aberrant configurations of cristae. The mitochondrial matrix contained sometimes spherical electron dense bodies different in size and vacuoles. Ring-shaped mitochondria were also observed. The most prominent ultrastructural feature, similarly as in daughter, was the occurrence of intramitochondrial highly ordered paracrystalline inclusions.

Neurones and microglia in central nervous system immune response to degenerative processes. Part 1: Alzheimer's disease and Lewy body variant of Alzheimer's disease. Quantitative study.

The quantitative correlation between neurone loss and brain immune response, assessed by intensity of microglia inflammatory reaction in cortical association area and limbic cortex, was investigated and compared in previously immunohistochemistry (IHC) and ultrastructural confirmed 11 cases of Alzheimer's disease (AD), 7 cases mixed form of Dementia with AD findings and Lewy bodies (AD/DLB) reported, in accordance with Consortium on Dementia, as Lewy body variant of AD (LBV) and 6 non-demented autopsy control cases from 63 to 86 years old. In the present work we investigated association and limbic cortical areas linked with memory mechanisms; there are regions characterised by early distribution of IHC confirmed AD and DLB/AD (LBV) markers, as well as a substantial physiological stability of neurone pool regardless of age. The results indicated that AD and LBV differ in their neurone loss intensity and inflammatory reaction, with much higher intensity in AD. In Alzheimer's disease, neurone loss in association temporal cortex made up 51% of control values with simultaneous 8-fold increase in the density of MHC II-positive activated microglia, whereas in LBV, both the loss of neurone density and the increase in activated microglia density, was not so high (up to 41% and 4-5-fold, respectively). Changes in the limbic cortex were less pronounced. A strong correlation in the clinical material between neurone loss and microglia activation in both processes, especially in AD (r = 0.73), speaks in favour of the hypothesis on the neuronal immune surveillance and arousal of immune brain response in conditions of declining control, due to significant neurone loss in the neurodegenerative process. The inflammatory reaction of MHC II-immunoreactive microglia, concomitant with neurodegenerative process, seems to be a consequence of increased immune response due to loss of neurones and weakening of their control upon immunosurveillance in central nervous system.

Major histocompatibility complex class II expression in the frontal and temporal lobes in the human fetus during development.

Antigen-presenting cells (APCs) that show the expression of major histocompatibility complex (MHC) class II molecules in adult persons are related to an early phase of immunological response. These molecules are responsible for the binding, transport, and presentation of a foreign antigen to helper T lymphocytes and determine the type of antibodies produced. They also stimulate the multiplication of specific B lymphocytes and participate in the elimination of autoreactive lymphocytes and maturation of T lymphocytes. Cells with MHC II molecules expressed on their surface were observed in the frontal and temporal lobes of 30 brains of human fetuses with normal development between gestation weeks (GW) 11 and 22. MHC II expression was noted during the whole interval under study. Its immunocytochemical localization was noted on the surface of the cerebral meninges cells, in the choroid plexus of the lateral ventricle and blood vessel lumen, and in ameboid microglia (AM) and ramified microglia (RM) cells in both cerebral lobes of the human fetus. The expression of MHC II that occurred on the cells of the central nervous system (CNS) already in GW 11 may be evidence not only of an early capability of immunological protection of the fetal nervous system, but also of a significant role potentially played by this system in normal embryogenesis. Despite continuous controversy over the cellular lineage of microglia origin, the expression of MHC II on AM and RM cells indicates its mesodermal origin, as in other APCs.

Phenotype of mast cells in the brain tumor. Capillary hemangioblastoma.

Mast cells (MC) are heterogenous cell population. In normal human brain they are not numerous. Increases in number of mast cells within CNS occur in certain disease states including neoplasms. In capillary hemangioblastoma several authors reported mast cells as a fourth cell type of the tumor. The aim of the present study was to examine phenotype and distribution of MC in cerebellar capillary hemangioblastoma by means of specific immunological markers. Study was performed on the tumor of ten affected individuals. Tumor specimens of seven cases were fixed in formalin and embedded in paraffin wax. Additional three tumours were fresh-frozen samples. Mast cells were identified with two monoclonal antibodies generated against tryptase and chymase. In all capillary hemangioblastomas mast cells were numerous exclusively in the tumor mass and only occasionally found in adjacent or far from the tumor located areas of the cerebellum. The cells contained tryptase and chymase. At periphery of hemangioblastomas some mast cells underwent degeneration and calcification. Our results confirm previous observations that mast cells are numerous in the capillary hemangioblastoma and show that most of these cells are tryptase/chymase phenotype (MCTC).

The significance of immunocytochemical markers, synaptophysin and neurofilaments in diagnosis of ganglioglioma.

Ganglioglioma is a tumor composed of neoplastic neurons and neoplastic glial cells mixed in different proportions. Astrocytes are the essential glial component. The tumor proliferates mostly in the temporal lobe cortex, scarcely in other areas of the brain. In ganglioglioma the population of ganglionic neurons is very difficult to diagnose. In the last ten years, immunocytochemical reaction with synaptophysin and neurofilament protein (NFP) triad considered as neoplastic neuron markers seemed to differentiate neoplastic nerve cells from normal neurons occurring incidentally within neoplastic proliferation area. In our study, the reaction with synaptophysin and NFP was performed on fragments of normal frontal lobe, pons and cerebellum as well as on fragments of post-operation tumor diagnosed as ganglioglioma. A positive synaptophysin reaction was obtained on the surface of neoplastic neurons in gangliogliomas, as well as on the surface of normal neurons in the encephalon, cerebellum and pons. Both neoplastic and normal neurons and their processes showed the expression of neurofilaments protein triad. Thus, a positive reaction of neurons with synaptophysin and NFP seems to be nonpathognomic in the diagnosis of the neoplastic neuron population in gangliogliomas.

Dysembryoplastic neuroepithelial tumor. A case report.

Dysembryoplastic neuroepithelial tumor (DNT) is a rare, benign tumor encountered in the cortex. It is characterized by the presence of cells of different histogenesis. Due to its mixed nature (glial-neuronal), WHO histological classification of brain tumors included it into the group of neuronal and glial-neuronal mixed tumors. Case of tumor in a 19-year-old woman experiencing for three years seizure of temporal lobe epilepsy is presented. A cranial magnetic resonance imaging (MRI) showed "pseudocystic" tumor in temporal lobe. Histological and immunocytochemical examinations of the tumor fragment removed during surgery revealed large numbers of neuronalglial nodules occurring in the cerebral cortex. Columns of glial-neuronal structures crossing parallely to the cortex surface, surrounded by oligodendrocyte-like cells (OLC) were a characteristic feature of the tumor texture. In the tumor interstitium, "floating" maturated, dysplastic-free ganglionic cells were visible in numerous bright spaces. In addition, numerous lobuliform--structured areas consisted of oligodendrocyte-like cells. Oligodendrocyte-like cells were characterized by positive immunoreaction to the presence of S-100 protein and synaptophysin. Basing on clinical manifestation and histopathological findings dysembryoplastic neuroepithelial tumor was diagnosed.

Electron microscopic and immunohistochemical verification of diagnosis in two archival cases recognized as encephalitis necroticans acuta (ENA) on routine examinations.

Two archival cases diagnosed 20 years ago on routine neuropathological methods as Encephalitis Necroticans Acuta (ENA) were investigated in EM and by immunohistochemical methods. The previous diagnosis was confirmed only in one case because Herpes simplex virus was found. In the second case the intracellular inclusions visible in ME corresponded to Measles Virus thus previous diagnosis was changed to SSPE.

The comparison of microglia maturation in CNS of normal human fetuses and fetuses with Down's syndrome.

The study was performed on the tissues derived from the central nervous system (CNS) of 72 normal human fetuses between 8 and 22 week of gestation (GW) and 30 fetuses with genetically confirmed Down's syndrome between 17 and 22 GW. Histochemical, immunocytochemical and ultrastructural examinations of microglial cells in frontal lobe, mesencephalon and cerebellum were carried out. A quantitative evaluation of developing microglia was performed in comparison with astroglial cells by counting the mean number of cells per 1 mm2. The study indicated that microglial cells emerge at the same time in all structures under study, both in normal fetuses and in those with Down's syndrome. It was also found that ameboid microglia (AM) and ramified microglia (RM) emerge at the same time and show the same morphological structure in both groups of fetuses. It was revealed that in the CNS of fetuses with Down's syndrome, the number of ramified microglial cells increased significantly as compared with in normal fetuses. Astroglial cells outnumbered microglial cells in the normal fetal development. Due to the enhanced number of RM cells in the CNS of fetuses with Down's syndrome the quantitative difference between these cells obliterated, and microglial cells in the frontal lobe cortex even outnumbered astroglial cells.

Multilocular cysticeral and hydatid cysts of the brain: a report of three cases.

Three cases of multilocular parasitic brain cysts are presented; two cases of specific form of neurocysticercosis and one case of multilocular hydatid cyst. MRI shows features seen in other cystic lesions of the CNS. In all cases the diagnosis was established by neurosurgical brain biopsy. The authors indicate that the parasitic disease should be taken into consideration in differential diagnosis of tumor-like cystic brain lesions.

Intractable epilepsy in children who develop epilepsy in the first decade of life--a prospective study.

Prospective studies on 347 children under treatment due to seizures which appeared in the first 10 years of life helped to evaluate and define the incidence of epilepsy resistant to treatment. With regard to each patient the following aspects were analysed: the kind of seizures, their etiology, accompanying neurological disorders and a type of epileptic syndrome, kind of treatment applied before admission to the clinical department as well as socioeconomic conditions of the families. Patients under study were divided into four age groups to evaluate the results. Epilepsy, which was completely resistant to treatment, was observed in 10% of the patients, partially resistant in 20%. Resistance is the outcome of the following factors: onset of epilepsy in early childhood, symptomatic etiology coexisting symptoms of CNS damage, occurrence of unfavourable epileptic syndromes such as Lennox-Gastaut, wrong selection and low dosage of drugs, inappropriate polytherapy and adverse social conditions. On the basis of the results obtained, the authors suggested point evaluation as a kind of screening in prediction of failures in treatment.

Adult schizophrenic-like variant of adrenoleukodystrophy.

A 35-year-old man died after 30 months following the onset of the disease. There was a history of changes in his mental condition, including disturbances of behavior as well as the evidence of progressing dementia. The patient revealed gait disturbances and finally became bed ridden. Bizarre behavior and changes of mood with concurrent growing irritability which predominated during the course of disease, may explain the initial diagnosis of schizophrenia. Then cerebellar and spastic movement disorders leading to paraparesis and sphincters disturbances developed. Clinical symptoms of adrenal failure were not found apart from episodes of arterial pressure fall. After two years a magnetic resonance imaging (MRI) revealed an extensive diffuse demyelinative process in white matter of cerebral and cerebellar hemispheres. Activity of lysosomal enzymes was normal. A general autopsy revealed atrophy of adrenal cortex and the presence of ballooned cells with striated cytoplasm in the reticular and fasciculate zones. Neuropathological examination revealed an extensive demyelination of white matter in cerebral and cerebellar hemispheres and of the long paths of the brain stem, corresponding to changes in MRI examination. Within demyelination areas damage of axons and diffuse cellular and fibrous gliosis were found as well as perivascular lymphocytic infiltrations with the presence of strong PAS (+) and Sudan (+) macrophages. Immunocytochemical reactions with HAM-56 and RCA1 in macrophages were positive. Electron microscopy examination revealed lamellar inclusions in cytoplasm of macrophages. Similar structures were present in the lysosomes of astrocytes. Morphological examination of adrenal glands as well as morphological and ultrastructural study of the brain allowed us to diagnose the cerebral form of adrenoleukodystrophy (ALD). Topography and character of the brain changes seems to be in keeping with a rare schizophrenic-like variant of ALD with progressive dementia. Abnormal plasma profile and increased VLCFA concentration in the patient's 13-year-old daughter confirm the ALD diagnosis.

Mitochondrial encephalomyopathy of mixed MELAS type.

A 27-year-old man with slowly progressing symptoms of pigmentary retinal degeneration, cerebellar, pyramidal and extrapyramidal syndrome and atrophy of lower limb muscles, was admitted to the Department of Neurology. During the final stage of disease, generalized, tonic and clonic seizures, absence and myoclonic epilepsy as well as Jackson's motor seizures were observed. A computed tomographic (CT) scan showed a considerable atrophy of cerebellum and pons. A magnetic resonance imaging (MRI) revealed diffuse cortical and subcortical atrophy, especially in structures of posterior intracranial fossa and bilateral foci of increased signal intensity in cerebral cortex and subcortical gray structures. A morphological study of a biceps specimen revealed the presence of so called ragged-red fibers characterized by abnormal mitochondria with paracrystalline inclusions. A considerable atrophy of the central nervous system, especially of cerebral and cerebellar cortex was revealed by a macroscopic study of the brain. Numerous focal and so called pseudolaminar cortical necroses in the brain, regardless of vascular supply, with characteristic proliferation of capillary vessels were predominating in a microscopic study. The clinical data and especially histopathological features count for the diagnosis of mitochondrial encephalomyopathy of MELAS type. The presence of additional features such as pigmentary retinal degeneration, characteristic of Kearns-Sayre syndrome and myoclonic seizures typical of MERRF syndrome allows the classification of this case as mixed MELAS syndrome.

Children who develop epilepsy in the first year of life: a prospective study.

A long-term prospective study was carried out of 133 children diagnosed as having epilepsy in the first year of life, of whom two-thirds had West syndrome and one-third had other forms of epilepsy. They were followed for a minimum of three years (half for over seven years), during which time 15 children died. Of the 118 surviving, 54 had an IQ of > 70, but 53 were severely mentally impaired, of whom two-thirds had West syndrome. Only 56 per cent currently have no seizures, and no significant differences were found in this respect between children with West syndrome and those with other forms of epilepsy. Regression in mental development occurred significantly more frequently among children with active epilepsy. These results lead to the conclusion that the degree and type of central nervous system damage existing at the onset of epilepsy is decisive for the outcome of the child, but the cessation of epileptic seizures also improves the child's developmental possibilities.

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.

Local and diffuse spread of juvenile cerebellar astrocytomas in subarachnoid space. Light and electron microscopic study.

Based on 5 cases of juvenile astrocytomas the unusual behaviour of this type of tumor is described. It is expressed by local and/or diffuse spread of the neoplasms in the subarachnoid space of the brain hemispheres, cerebellum and spinal cord. The light and electron microscopic examinations have revealed the morphological features of well differentiated tumors of astrocytic origin and of fibrillary type which in a great number of cases have a favourable prognosis. The cause of break through into the subarachnoid space, despite its morphology which indicates on a high degree of differentiation of the tumors, is not known. The relation of primary to secondary infiltration of the subarachnoid space or of the leptomeninges is discussed.

Brain growth in Down syndrome subjects 15 to 22 weeks of gestational age and birth to 60 months.

We have found similarities of skull shape, brain growth and brain maturation in 17 DS and 10 non-DS (control) fetuses, ages 15-22 weeks of gestational age (Group A), and differences in 101 DS and 80 non-DS cases, from birth to 60 months (Group B). Postnatally, the gross neuropathological differences between DS and control brains are more distinct after 3-5 months of age. The anterior posterior diameter fronto-occipital length of the brain hemispheres is shortened and that is secondary to reduction of frontal lobe growth. Also flattening of occipital poles, narrowing of the superior temporal gyruses and generalized retardation of brain growth were common findings. Standard morphometric methods indicate changes from birth [Wisniewski et al. 1984, 1986, 1990]. The cerebral cortex of the DS cases had a 20-50% reduction of neurons since birth, mainly in the granular layers [Wisniewski et al. 1984, 1986, 1990]. Changes in brain weight with age were greater in the non-DS than in the DS cases, and greater in males than in females. CHD and GI malformations were associated with less brain weight in both DS and non-DS cases. We suggest that the prenatal retardation of neurogenesis begins after 22 weeks' gestational age. The postnatal retardation of brain growth is secondary to pre- and postnatal abnormalities in synaptogenesis.