Congenital reticulum cell sarcoma of the cerebellum

Summary A case report, with autopsy findings, of a large circumscribed reticulum cell sarcoma of the cerebellum, in a 15 day-old female infant with clinical symptoms from the 8th day of life, and a review in tabular form of histologically confirmed primary intracranial sarcomas during the first year of life are presented. Among 200 intracranial tumours (except for teratomas) in infants up to one year of age, collected from the literature and a personal series of cases, primary sarcomas account for 9,5% and medulloblastomas for 15%. The relationship between cerebellar reticulum cell sarcoma and so-called medulloblastoma is briefly discussed. The aetiology of congenital intracranial neoplasms is unknown.

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Zusammenfassung Fallbericht über ein erst autoptisch verifiziertes großes, umschriebenes Reticulumsarkom des Kleinhirns bei einem 15 Tage alten weiblichen Säugling, der klinisch Symptome ab dem 8. Lebenstag geboten hatte. Eine Übersicht der histologisch gesicherten primären intrakraniellen Sarkome im ersten Lebensjahr wird in tabellarischer Form gegeben. Unter 200 intrakraniellen Geschwülsten — außer Teratomen — bei Neugeborenen und Säuglingen aus dem Weltschrifttum und einer eigenen Beobachtungsserie machen primäre Sarkome 9,5% und Medulloblastome 15% aus. Die Beziehungen zwischen Reticulumsarkom des Kleinhirns und sog. Medulloblastom werden kurz erörters. Die ätiologie angeborener Hirngeschwülste ist unbekannt.

     

Quantitative analysis of “synaptic” ribbon profiles in the pineal complex of male and female Pirbright-White guinea pigs

Summary Previous studies have pointed in the direction of sex differences as well as regional differences in the pineal gland of guinea pigs. In the present investigation these aspects were studied at the electron-microscopic level by quantitating different types of synaptic bodies, intrinsic to pinealocytes. The two major types of synaptic organelles, ribbons and spherules, did not exhibit regional or sex differences. Synaptic structures intermediate in appearance to ribbons and spherules were significantly larger in number in males in the distal region of the pineal gland, compared to females. As previous studies have shown that ribbon and spherule numbers undergo characteristic changes depending on the functional state of the pineal gland, it is concluded that, as far as the synaptic organelles are concerned, no clear-cut sex or regional differences appear to exist in the guinea pig pineal gland.     

Neuroectodermal tumors of the peripheral and the central nervous system share neuroendocrine N-CAM-related antigens with small cell lung carcinomas

Summary The current study describes the presence of neuroendocrine antigens of peripheral and central neural tumors using eight monoclonal antibodies raised to small cell lung carcinoma (SCLC), which recognize neural/neuroendocrine or neural antigens, as defined by their reaction pattern in normal tissues and tumors. At least five of them recognize different epitopes of the neural cell adhesion molecule (N-CAM). It was found that all of 12 neuroblastomas, 2 ganglioneuroblastomas and 4 ganglioneuromas as well as 23 central primitive neuroectodermal tumors, 13 astrocytomas and 4 ependymomas share neural/neuroendocrine antigens (as defined by the anti-N-CAM antibodies Moc-1,-21,-32,-52 and-191) with SCLC. The neural/neuroendocrine antigen defined by Moc-171 was also found in all peripheral tumors, but only in further differentiated central tumors. Non-N-CAM related neural antigens (as defined by Moc-51 and-172) were found only in better-differentiated peripheral and central tumors, but they could be demonstrated in all three medulloblastoma cell lines studied. In addition, the antigen defined by Moc-51 was demonstrated in an immunoblot of a neuroblastoma cell line. Antibodies recognizing epithelia antigens of SCLC and other epithelia and their tumors (Moc-31 and-181) were non-reactive. It was concluded that these findings give further support for a relation between neural and neuroendocrine tumors and that some of the antibodies may be useful for the detection of differentiation in neural tumors. Antibodies with an epithelia recognition pattern may serve to distinguish neural from neuroendocrine tumors.Supported by NIH grant CA 36245 W.M.M. was a Fullbright scholar     

Neuropathology of lissencephalies

The neuropathological findings at autopsy in four cases of type I and three of type II lissencephaly are presented. Type I lissencephaly is characterized by agyriapachygyria with a markedly thickened cerebral cortex with four coarse histological layers. The normally myelinated white matter, often with neuronal heterotopias, is very narrow, and the gray-to-white matter ratio is inverted (about 4:1); there are no white-gray interdigitations. Claustrum and capsula extrema are absent. Ventricular dilatation is present, especially of the occipital horns. In the hypoplastic brain stem large olivary heterotopias can often be observed. Severe cerebellar malformations, obstructive hydrocephalus, severe eye abnormalities, and congenital muscular dystrophy are not seen. Clinically, type I lissencephaly presents as isolated lissencephaly sequence or as Miller-Dieker syndrome with characteristic facial dysmorphism. The long survival of 20 years achieved by one of our patients is very uncommon. Type II lissencephaly is characterized by widespread agyria. Usually, obstructive hydrocephalus is present with a thin cerebral mantle showing a slightly thickened cortex and a narrow, hypomyelinated white matter often with neuronal heterotopias (gray-to-white matter ratio about 1:1). The border between gray and white matter is blurred. Claustrum and capsula extrema are absent. Histologically, the cortex appears disorganized without layering; widespread leptomeningeal gliomesenchymal proliferations and glioneuronal heterotopias are present. Hydrocephalus is caused by obstruction of the subarachnoid space, aqueductal stenosis, and Dandy-Walker malformation. The latter is a typical finding in type II lissencephaly together with severe cerebellar cortical dysplasias. Aplasia of the olfactory nerves, gliotic fusion of the frontal lobes, and an occipital cephalocele may be found. Type II lissencephaly occurs in clinical syndromes with severe eye abnormalities and congenital muscular dystrophy (the so-called Walker-Warburg syndrome). The congenital muscular dystrophies have no dystrophin deficiency, as we were able to show immunohistochemically in the muscle biopsies of two further patients with this syndrome.Presented at the Symposium on Lissencephaly and Related Disorders, Münster, Germany, 13 July 1992     

Immunohistochemical study on the distribution of α and β subunits of S-100 protein in brain tumors

Summary The immunohistochemical distribution of and subunits of S-100 protein (S-100, S-100, respectively) in 138 cases of human brain tumors was investigated by the avidin-biotin immunoperoxidase method. Brain tumors can be divided into four groups: group 1 [S-100 (+) and/or S-100 (+)]; astrocytoma, glioblastoma, ependymoma, subependymoma, oligodendroglioma, choroid plexus papilloma, gangliocytoma, meningioma, chordoma, malignant melanoma. Group 2 [S-100 (+) and S-100 (-)]; pineoblastoma, pituitary adenoma, craniopharyngioma, rhabdomyosarcoma. Group 3 [S-100 (-) and S-100 (+)]; acoustic Schwannoma. Group 4 [S-100 (-) and S-100 (-)]; medulloblastoma, malignant lymphoma, germinoma. The S-100 immunoreactivity pattern in brain tumors was similar to those obtained using conventional anti-S-100 protein sera. In the first group of brain tumors both the number of positively stained tumor cells and the staining intensity were generally greater for S-100 than for S-100 with a few exceptions including one gemistocytic astrocytoma, one subependymoma, one malignant melanoma, and some cases of glioblastomas. As to the relationship between malignancy and S-100 protein in glioma, S-100 immunoreactivity decreased according to degree of malignancy, while that of S-100 varied, suggesting a heterogeneity of tumor cells in glioblastomas. Immunostaining for S-100 and S-100 might become a useful diagnostic procedure in brain tumors and may give us more detailed and precise data of S-100 protein in brain tumors.     

Amyotrophic cerebellar hypoplasia

Summary Lower motor neuron degeneration, cerebellar hypoplasia, atrophy of pons, olives, and cerebellum, sclerosis of thalamus and pallidum, and deficient myelination were found in a 2-months-old baby with laryngeal paralysis, mental retardation, progressive amyotrophy, and slow nerve conduction velocity. Such changes seem characteristic of an unusual syndrome previously referred to as cerebellar hypoplasia in Werdnig-Hoffmann disease, or anterior horn cell disease with pontocerebellar hypoplasia. Although the pathologic changes in lower motor neurons are indistinguishable from those in other cases of infantile spinal muscular atrophy, the consistent reproducibility of a complex pathologic pattern suggests that this is probably a manifestation of a separate disease process. The term amyotrophic cerebellar hypoplasia (ACH) is a convenient designation for the syndrome.Supported in part by National Institutes of Health grant no. RR75     

Blood flow and metabolism in heterotopic cerebellar grafts during hypoglycemia

Summary Hypoglycemia-induced disturbances of brain metabolism and neuronal injury exhibit a distinct predilection for forebrain structures, in particular the caudate-putamen, hippocampus and cerebral cortex, whereas the cerebellum is remarkably resistant. In an attempt to assess the biological basis of this differential regional vulnerability, we have used a neural transplantation technique to compare hemodynamic and metabolic changes in cerebellum during servere hypoglycemia with those in heterotopic cerebellar grafts. To this end, the cerebellar anlage of fetal rat brain (day 15 of gestation) was stereotactically transplanted into the vulnerable caudate-putamen. Following a differentiation period of 8 weeks the grafts had developed into an organotypic population of mature cells with laminar histoarchitecture. Host animals were then subjected to insulin-induced hypoglycemia. After 15 min of isoelectric EEG, blood flow was increased throughout the brain but residual glucose consumption was significantly higher in cerebellum (0.29 mol/g per min) and cerebellar grafts (0.22 mol/g per min) as a result of increased glucose extraction. Hypoglycemia caused a depletion of ATP in all brain structures except cerebellum where normal levels were maintained. Correlation of local ATP content and glucose utilization revealed a threshold-like decline of ATP at a glucose utilization rate of 0.27 mol/g per min. ATP, in consequence, was normal in cerebellum but partially depleted in cerebellar grafts. It is concluded that the resistance of cerebellum to hypoglycemia is due to its capacity for higher glucose extraction at low blood glucose levels, and that this unique intrinsic property is preserved after heterotopic transplantation.Supported in part by the Deutsche Forschungsgemeinschaft (SFB 70)     

Experimental traumatic brain injury in rats stimulates the expression,production and activity of Alzheimer’s disease β-secretase (BACE-1)

Summary. Traumatic brain injury (TBI) is a risk factor for the development of Alzheimers disease (AD). After a traumatic brain injury depositions of amyloid beta (A) in the brain parenchyma were found. In this study we investigated the expression pattern of -secretase (BACE-1) in ipsi- or contralateral hippocampus and cortex following controlled cortical TBI in rats. BACE-1 mRNA levels, estimated by real time RT-PCR, were elevated 24h post injury, and persisting up to 72h, in the ipsi- and contralateral hippocampus and cerebral cortex as compared to the sham-treated animals (p<0.01). The TBI-induced changes in BACE-1 mRNA are due to enhanced hippocampal and cortical expression of BACE-1 mRNA in neurons and reactive astrocytes as revealed by in situ hybridization. The alterations in hippocampal BACE-1 mRNA levels are accompanied by corresponding increases in BACE-1 protein levels in ipsi- and contralateral hippocampus and ipsilateral cortex as demonstrated by Western blot analysis. In contrast, in the contralateral cortex only a weak increase of traumatically induced BACE-1 protein production was found. The activity of BACE-1 as measured by the formation of the cleavage product of amyloid beta precursor protein, transiently increased up to 48h after injury, but returned to basal level 7 days post injury. This study demonstrates that the -secretase is stimulated following TBI and may suggest a mechanism for the temporal increase of A levels observed in patients with brain trauma.     

Hyperkinetic children: Early indicators of potential school failure

Hyperkinetic children are identified as a population-at risk upon admission to kindergarten. The etiology of hyperkinetic behavior is controversial. Organic driveness, hyperkinetic behavior disorder, postencephalitic behavior, brain damage with behavioral and conceptual deficit, Strauss syndrome, have all been used to label essentially similar symptom constellations. Bypassing the area of controversy, a study is reported that demonstrates that children who were identified as hyperkinetic (using behavioral criteria developed in an earlier study) were (1) absent from school more frequently, and (2) did remarkably less well on standardized tests of school readiness than their peers rated nonhyperkinetic. The implications are discussed and suggestions made for the development of intervention programs.An earlier version of this paper was presented at the Annual Meeting of the American Orthopsychiatric Association, March, 1967.     

Gewebekulturuntersuchungen an experimentell erzeugten,transplantierten malignen Neurinomen

Zusammenfassung Zwei mit Äthylnitrosoharnstoff erzeugte maligne Neurinome unterschiedlicher Lokalisation und unterschiedlicher Morphologie wurden transplantiert. Im ersten Transplantat war die Morphologie der Primärgeschwulst noch weitgehend erhalten. Bei der Explantation dieser Geschwülste, sowohl in der Stückchenkultur als auch nach Trypsinierung, wurden in allen Fällen gleichartige Zelltypen beobachtet: Eine bipolare Spindelzelle und ein flach ausgebreiteter, großkerniger Fibroblast. Übergangsstufen, darunter eine makrophagenähnliche Rundzelle, besaßen Ähnlichkeit mit der Spindelzelle. Die Übereinstimmung dieser Befunde mit Ergebnissen der in-vitro-Kultur benigner Neurinome wird herausgestellt. Die bipolaren Spindelzellen werden als Schwannsche Zellen interpretiert.

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Tissue culture studies of experimentally induced transplanted malignant neurinomas

Summary Two malignant neurinomas induced with ethylnitrosourea, and of different localization and morphology were transplanted. The first transplants were morphologically very similar to the original tumor. In the explants of these tumors, whether obtained from the original tissue or after trypsination, similar cell types were observed: A bipolar spindle cell and a flat stretched fibroblast with a large nucleus. Intermediate forms, particularly a macrophage-like round cell had similarities with the bipolar cells. These results are consistent with earlier findings obtained with the in vitro culture of benign neurinomas. The bipolar spindle cells are considered to originate from Schwann cells.

     

Extracerebrale gliome im gesichtscbereich

Zusammenfassung Drei Fälle mit Gliomen im Gesichtsbereich werden geschildert und an Hand des vorliegenden Schrifttums die Pathogenese erörtert. Es handelt sich um Tumoren in der Stirnhöhle, am temporalen Augenunterlid und an der Retina. Alle Tumoren wurden vorweigend durch Astrocyten aufgebaut. Im Tumor des Augenunterlides wurden ferner markhaltige Nervenfasern und Ganglienzellen beobachtet. Da in den ersten beiden Fällen ein konnatales Auftreten angenommen werden konnte, wurde hier ein gleiches pathogenetisches Prinzip im Sinne einer frühembryonalen Encephalocelenbildung vermutet. Dabei muß sich neurogenes Gewebe abgespaltet haben. Nach der Geburt entwickelte sich ein blastomatöses Wachstum. Den Tumor der Stirnhöhle möchten wir den sogenannten nasalen Gliomen und den Tumor am Augenlid den sogenannten Retina-Anlage-Tumoren zuordnen. Bei dem von der Retina ausgehenden Gliom wird auf Grund des späten Manifestationsalters und der Tendenz zur Cystenbildung ein Tumor im Sinne eines cerebralen Astrocytoms vermutet.

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Extracerebral gliomas in the facial region

Summary Three cases of gliomas in the facial region have been presented and with a review of literature their pathogenesis was discussed. The tumors were localized in the sinus frontalis, the temporal lower eyelid, and in the vitreous body in connection with the retina. All tumors consisted mainly in astrocytes. In the tumor of the lower eyelid additional myelinated nerve fibres and nerve cells were seen. The first two cases probably were of connatal origin and therefore a common pathogenetic principle was suggested. We supposed an encephalocele-like herniation in the early fetal development. At the same time neurogenic tissue could have been separated. Postnatally, the tissue showed a blastomatous development. We include the tumor of the sinus frontalis in the nasal gliomas and the tumor of the lower eyelid in the retina-anlage-tumors. We suggested that the third tumor, which was fixed on the retina, was comparable with a cerebral astrocytoma because of the age of manifestation and the tendency to develop cysts.

Gewidmet Herrn Prof. Dr. B. Ostertag zum 75. Geburstag.     

Presence of apolipoprotein E on extracellular neurofibrillary tangles and on meningeal blood vessels precedes the Alzheimer β-amyloid deposition

The localization of apolipoprotein E (ApoE) has been examined immunohistochemically in the autopsied brains of middle-aged and old-aged control subjects, with and without amyloid protein (A) deposits, and of Alzheimer's disease patients. Senile plaques were consistently labeled with ApoE antiserum even in the very early stage of senile plaque formation seen in the fifth decade. In the cerebellar molecular layer, small dots of ApoE immunoreactivity, which were prominent in the Alzheimer's disease subjects, were observed in addition to immunoreactivity in diffuse plaques. ApoE antisera labeled all of the extracellular neurofibrillary tangles (NFT), whereas only a small minority of extracellular NFT were positive for A. A punctate pattern of ApoE immunoreactivity was seen at the media of the meningeal vessels lacking amyloid, when senile plaques were present in the nearby cortex. In the early stage of amyloid angiopathy, the distribution of ApoE immunoreactivity was much more extensive than that of A positivity. These findings suggest that ApoE accumulates in the early stage of senile plaque formation and, furthermore, that ApoE accumulation precedes A deposition in extracellular NFT and amyloid angiopathy.     

Extensive surgical excision of large hemispheric “malignant” astrocytoma in a 6-week-old infant

A massive hemispheric high-grade astrocytoma, diagnosed in a 6-week-old infant, was totally excised by means of two craniotomies. The child is still alive and well with minimal neurological dysfunction 1.5 years after operation. This case report illustrates the benefit of aggressive surgical excision (without radiation or chemotherapy) of massive malignant neonatal astrocytomas. While surgical deficits may be minimized by the plasticity of the developing nervous system, extensive excision may yield occasional long-term palliation.     

A lipoma of the cerebellum

A lipoma, essentially occupying the superior vermis and related to a branch of the left superior cerebellar artery, was an incidental finding at autopsy of a 75 year old woman who died of renal failure. Localisation of a lipoma to the superior vermis seems to be rare. Besides fatty tissue there were cartilaginous components. Malformation of the convolutional pattern in the immediate vicinity of the tumour suggests its origin from a false mixture of tissue (hamartoma) in the anlage of the cerebellum.     

Neuropsychological and EEG evaluation in exposure to trichloroethylene

Summary After 1 year of exposure to trichloroethylene, reversible neuropsychological impairment and persistent EEG paroxysms were observed in one patient. The improvement of neuropsychological performances and the persistence of severe EEG abnormalities after withdrawal of the toxin suggest functional cerebral damage after prolonged exposure to trichloroethylene.     

Comparison of integrin adhesion molecules expressed by primary brain lymphomas and nodal lymphomas

The expression of 17 adhesion molecules was immunohistochemically examined in 5 primary cerebral lymphomas (PCL) and in 5 histologically similar nodal lymphomas (NL) to evaluate their possible involvement in selective targeting of lymphoma cells to the brain. PCL and NL tumor cells showed very similar expression patterns: they were consistently positive for ₃, ₄ and ₁ integrin chains; negative for ₂, ₆, ₃ and ₄ integrin chains; and heterogeneous for ₅, _L, _M, _X, ₂ and ₇ integrin chains, as well as for intercellular adhesion molecule-1 (ICAM-1) and the selectin LECAM-1. Loosely infiltrating PCL showed lower levels of the _L2 integrin than compact cell clusters. Vessels stained for ICAM-1 and vascular cell adhesion molecule-1 (VCAM-1). We conclude that the adhesion molecules implicated in the extravasation of non-neoplastic leukocytes (₄₁/VCAM-1 and _L2/ICAM-1) are also expressed by both PCL and NL. The adhesion molecules examined are apparently not selective mediators of lymphoma cell homing to the brain, but at least _L2 integrin might be related to the infiltration pattern of PCL within the brain parenchyma.Supported by the Sander Foundation     

Pure post–stroke cerebellar cognitive affective syndrome: a case report

Abstract. Cerebellar pathology commonly shows important motor signs and less evident cognitive dysfunction. The cerebellar cognitive affective syndrome is characterised by impairment on executive function, spatial cognition, language and behaviour. We report the case of a man with acute onset of transitory motor features and severe mental disorders. Cranial CT and brain MRI revealed extended cerebellar lesions. Neuropsychological assessment disclosed deficits of attention, executive function and memory. Auditory event–related potentials showed abnormal P300. These data suggest a pure cerebellar cognitive affective syndrome and strengthen the hypothesis of cerebellar cognitive function modulation.     

Immunohistochemical demonstration of vimentin in human cerebral tumors

Summary The distribution of vimentin (VIM) has been histochemically investigated in 53 cerebral tumors and compared in gliomas to that of glial fibrillary acidic protein (GFAP). In gliomas VIM is less positive than GFAP, but shows the same distribution. It cannot be considered as indicating immaturity of glial tumor cells. VIM is also positive in glial processes of cerebellar pilocytic astrocytomas, in Schwann cells of neurinomas and in endothelial cells of all oncotypes. In medulloblastomas, VIM decorates reactive glia cells. A diffuse positive reaction has been observed in meningiomas. In hemangioblastomas, besides intervascular and endothelial cells, groups of polygonal cells are intensely positive for both VIM and GFAP. The interpretatiên of VIM in cerebral tumors is largely based on the distribution patterns of this intermediate filament in the developing CNS of rodents.Supported by a grant of the Italian National Research Council, Special Project Oncology, contract number 84.00796.44. and by the Italian Association for Cancer Research (A.I.R.C.)     

Cortical regulation of subcortical dopamine systems and its possible relevance to schizophrenia

Summary A unique model of DA system regulation is presented, in which tonic steady-state DA levels in the ECF act to down-regulate the response of the system to pulsatile DA released by DA cell action potential generation. This type of regulation is similar in many respects to the phenomenon proposed to mediate the action of norepinephrine on target neurons; i.e., an increase in the signal-to-noise ratio as measured by postsynaptic cell firing (Freedman et al., 1977; Woodward et al., 1979). However, in this model the signal and the noise are neurochemical rather than electrophysiological. Furthermore, the noise (tonic DA in the ECF) actually down-regulates the signal (phasic DA release) directly, and thereby provides a signal of its own that affects the system over a longer time-course. Therefore, the difference between signal and noise may also depend on the time frame under which such determinations are made.     

Somatosensory evoked potentials in patients with thalamic lesions

Summary Somatosensory evoked potentials (SEPs) were recorded in 20 patients with thalamic lesions confirmed by CT (10 with infarction, 10 with haemorrhage). The changes in SEP configuration are discussed in their relationship to clinical symptoms. Four types of SEP abnormality produced by thalamic lesion are distinguished: (1) FF type, (2) N20/P23 dissociation type, (3) N18/N20 false shift type, and (4) reduced early component type. It was shown that clinically similar lesions might produce different SEP patterns.