Pediatric rhabdoid meningioma: a morphological,immunohistochemical, ultrastructural and molecular case study

Rhabdoid meningioma is an uncommon meningioma variant categorized as WHO grade III. The majority of cases occur in adulthood. Herein, we describe a right fronto‐temporal rhabdoid meningioma affecting a 3‐year‐old boy. The lesion measured approximately 4 cm in diameter and incorporated the ipsilateral middle cerebral artery. Sub‐total surgical excision of the mass was performed. Histologically, the tumor was mainly composed of globoid plump cells with inclusion‐like eosinophilic cytoplasm, peripheral nuclei, prominent nucleoli and occasional intra‐nuclear cytoplasmic pseudo‐inclusion. The cells appeared in many areas loosely arranged and focally disclosed a papillary architecture. At immunohistochemistry, the tumor cells were EMA, vimentin, HHF35, PgR, INI‐1 and p53 positive. The proliferative index (Mib‐1) was 15% in the most positive areas. Ultrastructurally, tumoral cells showed an abundant cytoplasm, which was filled with numerous intermediate filaments. Desmosomal junctions were seen. RT‐PCR revealed the presence of NF2 gene expression. Molecular study did not indicate alterations of the INI‐1 gene, whereas it showed the presence of Pro72Arg in exon 4 at heterozygous state in the TP53 gene. Morphologic features along with immunohistochemical, ultrastructural and molecular results were consistent with the diagnosis of rhabdoid meningioma. The patient was treated with chemotherapy. The lesion remained stable after 33 months of follow‐up. Rhabdoid meningiomas rarely occur in children. Owing to its rarity, each new case should be recorded to produce a better clinical, pathological, molecular, prognostic and therapeutic characterization of this lesion.     

Brachial plexus meningioma,report of a case with immunohistochemical and ultrastructural examination

Summary Peripheral nerve meningiomas are exceedingly rare neoplasms of controversial origin; only four cases have been reported. Proposed origins of ectopic meningiomas include extradural trapping of arachnoid cells during embryogenesis, ectopic migration of arachnoid cell nests with the developing peripheral nerve, and metaplasia of mature peripheral nerve sheath cells or a common progenitor cell. In this report of a meningioma of the brachial plexus, immunohistochemical and ultrastructural examinations of the tumor matched all the criteria of a traditional meningioma but failed to clarify the origins of such neoplasms.     

Sclerosing meningioma: immunohistochemical analysis of five cases

Sclerosing meningioma is a rare morphologic subtype of meningioma and may be mistaken for atypical or malignant meningioma and astrocytoma or schwannoma because of marked collagen deposits and a sparse population of cells with little resemblance to meningothelial cells. Authors describe the histopathologic and immunophenotypic features of five cases of sclerosing meningioma. Histologically, all the cases consisted of paucicellular collagenous tissue containing spindle cells with or without small foci of meningothelial cell proliferation. The morphology and immunohistochemical profile of the spindle cells were different from those of conventional meningothelial cells. The meningothelial cells showed a typical immunoreactivity of conventional meningiomas, while the spindle cells displayed a strong expression of vimentin. The Ki-67 labelling index was uniformly low in all cases, and none of cases expressed p53 protein. In summary, the recognition of meningothelial cells in massively sclerotic lesions is helpful for a correct diagnosis. In the cases with a total absence of meningothelial cells, however, the vague collagenous whorls are more diagnostic rather than immunohistochemistry. Considering association with clear cell meningioma, prospective and retrospective long-term follow-up is necessary for deciding whether reminiscent clear cell meningiomas should be separated from sclerosing meningioma or not.     

Cerebellar liponeurocytoma: Morphological,immunohistochemical, and ultrastructural study of a relapsed case

Cerebellar liponeurocytoma is a rare and newly identified neoplasm found in adults which is reputed to be benign. Its salient morphological characteristics are advanced neuronal/neurocytic differentiation, the presence of lipomatous areas, low mitotic rate, and the absence of necrosis, pleomorphism and vascular hyperplasia. Reported is a case of relapsing liponeurocytoma which occurred 3 and a half years after the radical excision of the primary lesion. Histopathological aggressive features (mitoses and a high proliferation index as evaluated by MIB‐1) were shown in the primary lesion and recurrence of the tumor. We suggest that liponeurocytoma is an uncertain malignant potential lesion when mitoses are present and the MIB‐1 positive cells are more than 10%.     

Organisation of the cerebellar nucleus of the dogfish,Scyliorhinus canicula L.: A light microscopic,immunocytochemical, and ultrastructural study

Elasmobranchs possess a well-developed cerebellum with an associated cerebellar nucleus. To determine whether the organization of this nucleus is comparable with that of the deep cerebellar nuclei of mammals, we studied the dogfish cerebellar nucleus with light microscopic methods (Nissl stain, Golgi method, reduced silver stain, NADPH-diaphorase histochemistry and immunocytochemistry) and with electron microscopy. We found the dogfish cerebellar nucleus to consist of about 1,050 large neurons, the ratio of Purkinje cells to cerebellar nucleus neurons being about 17:1. Immunocytochemistry showed large glutamatergic neurons in the main portions of the nucleus and small glutamate- and/or α-aminobutyric acid (GABA)-immunoreactive cells in the subventricular region of the nucleus. Large glutamatergic neurons corresponded to bipolar or triangular cells revealed by Golgi methods. Application of horseradish peroxidase to the cerebellar cortex produced the labelling of beaded fibres of Purkinje cells in the cerebellar nucleus. Unlike in mammals, GABAergic innervation of the cerebellar nucleus was scarce: Purkinje cell axon terminals in the cerebellar nucleus did not appear to be GABA-immunoreactive, most GABAergic fibres being found in the subventricular neuropile. Some fibres immunoreactive to serotonin and somatostatin were also observed in the subventricular neuropile of the cerebellar nucleus. Three neuron types were distinguished with electron microscopy (types A to C). Type A cells were abundant and smooth-surfaced, and appeared to correspond to Golgi-impregnated neurons and large glutamate-immunoreactive cells. Type B neurons were scarce and possessed dendrites covered by sessile or stalked spines. Type C neurons were small cells located mainly in the medialmost region of the nucleus and corresponded to subventricular glutamate- and GABA-immunoreactive cells. Six types of synaptic bouton were observed (types I to VI). The most abundant (type I boutons) made symmetrical contacts and appeared to correspond to Purkinje cell axons. Type I boutons were the only type observed on perikarya and initial axon segments of type A cells. Type IV and type V boutons made complex glomerular-like asymmetrical contacts with spines of type B cells. Type VI boutons appeared to correspond to peptidergic and/or monoaminergic axons. The functional significance of these results is discussed. © 1996 Wiley-Liss, Inc.     

Congenital choroid plexus papilloma: light and electron microscopic study of a case

The outcome of a light and electron microscopic study of a congenital choroid plexus papilloma removed from a lateral cerebral ventricle of a 10-day-old male presenting hypertensive hydrocephalus at birth is reported. The tumor was diagnosed by CT and cerebral angiography. The findings, compared with those obtained from choroid plexuses of controls subjected to hemispherectomy for epilepsy, highlight the intense metabolic activity of the papilloma and the relevance of this to the communicating hydrocephalus that is frequently associated with it.

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Sommario Gli autori riportano i risultati di una indagine ottica ed ultrastrutturale eseguita in un caso di papilloma congenito, accompagnato da idrocefalia, del plesso corioideo del ventricolo laterale destro, asportato chirurgicamente in decima giornata di vita. Come controllo sono stati utilizzati i dati ottenuti da plessi corioidei normali prelevati in bambini sottoposti ad intervento di emisferectomia per epilessia. L'interesse per tale raffronto deriva dalla discussione ancora aperta sulle proprietà secretive del papilloma del plesso corioideo e sulle sue relazioni con il plesso corioideo normale.

     

Fibrous meningeal tumours with extensive non-calcifying collagenous whorls and glial fibrillary acidic protein expression: the whorling-sclerosing variant of meningioma

Meningiomas comprise a wide range of morphological patterns. We describe unusual fibrous meningeal tumours in two patients, composed of extensive non-calcifying collagenous whorls of varying size, resembling non-calcified psammoma bodies, while interposed tumour cells are sparse. Immunohistochemistry showed expression of S-100, vimentin and glial fibrillary acidic protein, whereas only single tumour cells stained for epithelial membrane antigen. Electron microscopy detected desmosomes or desmosome-like structures in both specimens. We conclude that these tumours represent a peculiar whorling-sclerosing variant of fibrous meningioma. Recognition of this meningioma variant is important in the differential diagnosis of meningioma versus other fibrous tumours of the meninges, including solitary fibrous tumours of the meninges, unusual forms of desmoplastic gliomas or chondroid tumours.     

Papillary meningioma: an aggressive variant meningioma with clinical features and treatment: a retrospective study of 10 cases

Introduction: Papillary meningioma is a rare subtype of malignant meningiomas. The aim of this retrospective study was to investigate the clinical, radiological, histopathological features and prognosis for papillary meningioma at our institutions. Materials and methods: Ten patients with clinically, radiologically and histopathologically confirmed papillary meningiomas were treated at our hospitals. The clinical data, imaging characteristics, histopathological features, surgical treatment and postoperative follow-up, were analyzed retrospectively. Results: The patients with a mean age of 36.9 years at the time of their initial operations. The papillary meningiomas were predominantly located in the convexity (n = 6). At their initial operation, six patients underwent gross total resection and four patients underwent subtotal resection. The mean post-operative follow-up period was 42.6 months (range: 12–90 months). Six patients underwent multiple surgical resections. The mean time to first recurrence was 21.5 months. On magnetic resonance imaging scan, marked enhancements and dural tail signs were displayed in all lesions. All lesions showed peritumoral edema. Cysts were seen in four lesions. Bone hyperostosis or destruction was seen in six lesions. Cerebrospinal fluid dissemination was seen in three lesions. Incomplete surgical resection was associated with recurrence. MIB-1 labeling index was associated with progression-free survival for patients (p = 0.0442). Conclusions: Papillary meningioma has a tendency to present in middle-aged patients, and it has specific clinical and histopathological characteristics. MIB-1 labeling index and the extent of resection might predict the recurrence. Cystic formation, peritumoral edema, osseous change and CSF dissemination might be neuroimaging characteristics of papillary meningioma, especially in recurrence papillary meningioma.     

A case of cerebral composite ganglioneuroblastoma: an immunohistochemical and ultrastructural study

Summary An unusual cerebral tumor is reported in a 14-year-old boy. On light and electron microscopy, the constituent cells were very complex; the majority of the neoplastic cells were primitive neuroectodermal cells dispersed in myxomatous or fibrous stroma. Neoplastic neuronal cells and hypertrophic astrocytes were also observed in these areas. The neuronal cells showed a continuous spectrum of differentiation from very primitive to mature ganglion cells. Furthermore, the tumor contained a highly cellular discrete area consisting of neuroblasts and their precursor cells. From these findings, a diagnosis of composite ganglioneuroblastoma was made.     

Light microscopic and ultrastructural analysis of GABA-immunoreactive profiles in the monkey spinal cord

It is hypothesized that terminals containing gamma-aminobutyric acid (GABA) participate in presynaptic inhibition of primary afferents. To date, few convincing GABA-immunoreactive (GABA-IR) axo-axonic synapses have been demonstrated in support of this theory. The goal of this study is to document the relationship between GABA-IR profiles and central terminals in glomerular complexes in lumbar cord of the monkey (Macaca fascicularis). In addition, the relationship between GABA-IR profiles and other neural elements are analyzed in order to better understand the processing of sensory input in the spinal cord. GABA-IR cell bodies were present in Lissauer's tract (LT) and in all laminae in the spinal gray matter except lamina IX. GABA-IR fibers and terminals were heavily concentrated in LT; laminae I, II, and III; and present in moderate concentration in the deeper laminae of the dorsal horn, ventral horn (especially in association with presumed motor neurons), and lamina X. Electron microscopic analysis confined to LT and laminae I, II, and III demonstrated GABA-IR cell bodies, dendrites, and myelinated and unmyelinated fibers. GABA-IR cell bodies received sparse synaptic input, some of which was immunoreactive for GABA. The majority of the synaptic input to GABA-IR neurons occurred at the dendritic level. Furthermore, the presence of numerous vesicle-containing GABA-IR dendrites making synaptic interactions indicated that GABA-IR dendrites also provided a major site of output. Two consistent arrangements were observed in laminae I-III concerning vesicle-containing GABA-IR dendrites: 1) they were often postsynaptic to central terminals and 2) they participated in reciprocal synapses. The majority of GABA-IR axon terminals observed contained round clear vesicles and varying numbers of dense core vesicles. Only on rare occasions were GABA-IR terminals with flattened vesicles observed. GABA-IR terminals were not observed as presynaptic elements in axo-axonic synapses; however, on some occasions, GABA-IR profiles presumed to be axon terminals were observed postsynaptic to large glomerular type terminals. Our findings suggest that a frequent synaptic arrangement exists in which primary afferent terminals relay sensory information into a GABAergic system for further processing. Furthermore, GABA-IR dendrites appear to be the major source of input and output for this inhibitory system. The implications of this GABAergic neurocircuitry are discussed in relation to the processing of sensory input in the superficial dorsal horn and in terms of mechanisms of primary afferent depolarization (PAD).     

Clinicopathologic features and pathogenesis of melanocytic colonization in atypical meningioma

Only two prior cases of benign dendritic melanocytes colonizing a meningioma have been reported. We add a third case, describe clinicopathologic features shared by the three, and elucidate the risk factors for this very rare phenomenon. A 29 year‐old Hispanic woman presented with headache and hydrocephalus. MRI showed a lobulated enhancing pineal region mass measuring 41 mm in greatest dimension. Subtotal resection of the mass demonstrated an atypical meningioma, WHO grade II, and the patient subsequently underwent radiotherapy. She presented 4 years later with diplopia, and MRI showed an enhancing extra‐axial mass measuring 47 mm in greatest dimension and centered on the tentorial incisura. Subtotal resection showed a brain‐invasive atypical meningioma with melanocytic colonization. The previous two cases in the literature were atypical meningiomas, one of which was also brain invasive. Atypical meningiomas may be at particular risk for melanocytic colonization as they upregulate molecules known to be chemoattractants for melanocytes. We detected c‐Kit expression in a minority of the melanocytes as well as stem cell factor and basic fibroblast growth factor in the meningioma cells, suggesting that mechanisms implicated in normal melanocyte migration may be involved. In some cases, brain invasion with disruption of the leptomeningeal barrier may also facilitate migration from the subarachnoid space into the tumor. Whether there is low‐level proliferation of the dendritic melanocytes is unclear. Given that all three patients were non‐Caucasian, meningiomas in persons and/or brain regions with increased dendritic melanocytes may predispose to colonization. The age range spanned from 6 years old to 70 years old. All three patients were female. The role of gender and estrogen in the pathogenesis of this entity remains to be clarified. Whether melanocytic colonization may also occur in the more common Grade I meningiomas awaits identification of additional cases.     

Rosenthal fibres: an immunohistochemical,ultrastructural and immunoelectron microscopic study

Summary The nature of Rosenthal fibres (RF) was investigated in eight cases each of low-grade astrocytoma and reactive gliosis using immunohistochemical (IH) staining for glial fibrillary acidic protein (GFAP), electron microscopy (EM) and immunoelectron microscopy (IEM) by immunogold labelling technique. By IH under light microscopy (LM), three types of RF were seen, uniformly positive (type I), rim positive (type II) and completely negative (type III). EM showed variation in structural pattern of RF. Some RF contained large amount of glial filaments (GF) intermingled with RF while others with a large amount of electron dense material and less GF. Thus, the presence and amount of GF in RF appear to be responsible for the different types of IH staining under LM. IEM showed that all RF including the ones consisting of entirelh amorphous material possess immunoreactivity for GFAP.It is suggested that RF formation is a two-stage process, staring with excessive accumulation of GF within astrocytic processes followed by their gradual alteration into electron-dense amorphous material under the influence of some unknown metablic or other factors. The quantitative analysis of different types of RF suggests a difference in the rate of formation of RF in neoplastic and reactive conditions.     

Intraventricular metaplastic meningioma in a child: case report and review of the literature

Childhood meningiomas are rare and display important differences from adult forms. We report the first case of an intraventricular metaplastic meningioma arising in a child. A 7‐year‐old female underwent resection of an enhancing tumor arising within the left lateral ventricle. It was composed of monomorphic cells embedded within an abundant myxoid stroma. The cells demonstrated epithelial membrane antigen and vimentin immunoreactivity. Ultrastructural analysis demonstrated intermediate filaments, complex intercellular interdigitations and desmosomes, and a diagnosis of myxoid (metaplastic) meningioma was rendered. This case reflects the higher incidence of intraventricular meningiomas in childhood and greater incidence of intraventricular meningiomas in the left lateral ventricle. Recognition of the grade I myxoid meningioma in this case is paramount since chordoid meningiomas, which share similar histologic features, are of a higher grade and worse prognosis.     

A combined flat-embedding,HRP histochemical method for correlative light and electron microscopic study of single neurons

A simple and reproducible method is described for studying the morphology of the same neuron at the light and electron microscopic level. This method utilizes horseradish peroxidase histochemistry and a recently described flat-embedding procedure wherein thin, aldehyde-fixed sections are placed in resin between glass microscope slides pretreated with dimethyldichlorosilane. The significance of these combined methodologies for correlative light and electron microscopic studies of single neurons is discussed.     

Rhabdoid papillary meningioma: A clinicopathologic case series study

World Health Organization (WHO) grade III meningiomas are subclassified on the basis of their architectural pattern into papillary and rhabdoid subtypes. Some meningiomas even combine papillary architecture with rhabdoid cytology. Additionally, they always show malignant histological features, follow an aggressive clinical course and tend to spread through the CSF after frequent local recurrence. We render the first series of rhabdoid papillary meningioma with review of the literature to further elucidate its biological behavior. From six patients (three male, three female), nine specimens of rhabdoid papillary meningioma were obtained between 1994 and 2010. Correlations of histologic parameters, immunohistochemical study, and clinical features were assessed. The mean age of patients was 44.7 years at their first operation. The mean postoperative follow‐up period was 63.2 months. Five patients experienced tumor recurrence, and one of them died from the disease after diffuse leptomeningeal dissemination. The mean time to first recurrence was 28 months. Only one patient was free of tumoral recurrence after an 8‐year follow‐up. Immunohistochemically, all tumors were positive for vimentin and epithelial membrane antigen. MIB‐1 labeling indices were higher following tumor recurrence. The present study expands the clinicopathologic horizon of rhabdoid papillary meningioma and suggests that it will behave aggressively based on its histology and concomitant features of atypia or malignancy or high MIB‐1 labeling indices. Close follow‐up and aggressive treatments of these tumors are warranted.     

The subnuclear organization of the rat interpeduncular nucleus: a light and electron microscopic study

The subnuclear organization of rat interpeduncular nucleus (IPN) has been examined by light microscopy following staining with Nissl and Holmes methods, 3H-leucine autoradiography, acetylcholinesterase (AChE), and cytochrome oxidase histochemistry on plastic sections stained with toluidine blue, and by electron microscopy. Three unpaired and four paired subnuclei are recognized. The rostral subnucleus is heavily stained for AChE, which clearly delineates its borders. It is distinguished ultrastructurally by two types of synapses on dendrites, and two on perikarya. Of the former, one type is formed by presynaptic processes which contain spherical and dense-cored vesicles and make asymmetrical contacts. Dense-cored vesicles are observed in many of the postsynaptic dendrites. A second type has presynaptic processes containing small, pleomorphic vesicles which make symmetrical contacts. Synapses on perikarya are found in the rostral, central, intermediate, lateral, and interstitial subnuclei. The dorsal subnucleus is continuous with the serotonin-containing B8 cells. The central subnucleus is distinguished by longitudinally oriented medial habenular axons separating palisades of cell bodies. These axons, which also traverse the intermediate subnuclei, form en passant S synapses with small dendrites of the central subnucleus. The intermediate subnuclei react faintly for AChE and intensely for cytochrome oxidase. They contain crest synapses formed by two habenular afferents, one from each medial habenula, which contact a narrow dendritic process en passant. The lateral subnuclei react intensely for AChE and have ultrastructural features similar to the rostral subnuclei. The interstitial subnuclei lie within each fasciculus retroflexus as it enters IPN. The small dorsal lateral subnuclei are evident by light microscopy.     

Tuber and subependymal giant cell astrocytoma associated with tuberous sclerosis: an immunohistochemical,ultrastructural, and immunoelectron microscopic study

The cellular nature of the giant eosinophilic cells of tuber and of the cells comprising subependymal giant cell astrocytoma (SEGA) in tuberous sclerosis (TS) remains unclear. To assess the characteristics of these lesions, 13 tubers and 6 SEGA were immunohistochemically studied with glial and neuron-associated antigens. In addition to conventional ultrastructure, 6 tubers and 8 SEGA were fibrillary acidic protein (GFAP) and somatostatin. Eosinophilic giant cells of tubers were positive for vimentin (100%), GFAP (77%) and S-100 protein (92%); such cells were also found to a various extent to be reactive for neuron-associated antigens, including neurofilament (NF) proteins (38%) or class III -tubulin (77%). SEGA also showed variable immunoreactivity for GFAP (50%) or for S-100 protein (100%); NF epitopes, class III -tubulin, and calbindin 28-kD were expressed in 2 (33%), 5 (83%) and 4 (67%) cases, respectively. Cytoplasmic staining for somatostatin (50%), met-enkephalin (50%), 6-hydroxytryptamine (33%), -endorphin (33%) and neuropeptide Y (17%) was noted in SEGA, but not in tubers. Ultrastructurally, the giant cells of tubers and the cells of SEGA contained numerous intermediate filaments, frequent lysosomes and occasional rectangular or rhomboid membrane-bound crystalloids exhibiting lamellar periodicity and structural transition to lysosomes. Some SEGA cells showed features suggestive of neuronal differentiation, including stacks of rough endoplasmic reticulum, occasional microtubules and a few dense-core granules. Furthermore, in one case of tuber, a process of a single large cell was seen to be engaged in synapse formation. Intermediate filaments within a few cells of both lesions were decorated by gold particle-labeled GFAP antiserum. Within the tumor cells of SEGA, irregular, non-membrane-bound, electron-lucent areas often contained somatostatin-immunoreactive particles, whereas the latter could not be detected in tuber. The present study provides further evidence of divergent glioneuronal differentiation, both in the giant cells of tubers and the cells of SEGA. The findings of similar cells at different sites, including the subependymal zone, white matter (heterotopias), and cortex indirectly supports the idea that these lesions of TS result from a migration abnormality.     

Quantitative and ultrastructural study of serotonin innervation of the globus pallidus in squirrel monkeys

The present immunohistochemical study was aimed at characterizing the serotonin (5‐HT) innervation of the internal (GPi) and external (GPe) pallidal segments in the squirrel monkey (Saimiri sciureus) with an antibody against the 5‐HT transporter (SERT). At the light microscopic level, unbiased counts of SERT+ axon varicosities showed that the density of innervation is similar in the GPi (0.57 ± 0.03 × 10⁶ varicosities/mm³ of tissue) and the GPe (0.60 ± 0.04 × 10⁶), with the anterior half of both segments being more densely innervated than the posterior half. Dorsoventral and mediolateral decreasing gradients of SERT varicosities occur in both pallidal segments, but are statistically significant only in the GPi. The neuronal density being significantly greater in the GPe (3.41 ± 0.23 × 10³ neurons/mm³) than in the GPi (2.90 ± 0.11 × 103), the number of 5‐HT axon varicosities per pallidal neuron was found to be superior in the GPi (201 ± 27) than in the GPe (156 ± 26). At the electron microscopic level, SERT+ axon varicosities are comparable in size and vesicular content in GPi and GPe, where they establish mainly asynaptic contacts with unlabeled profiles. Less than 25% of SERT+ varicosities display a synaptic specialization, which is of the symmetrical or asymmetrical type and occurs exclusively on pallidal dendrites. No SERT+ axo‐axonic synapses are present, suggesting that 5‐HT exerts its well‐established modulatory action upon various pallidal afferents mainly through diffuse transmission, whereas its direct control of pallidal neurons results from both volumic and synaptic release of the transmitter.     

Brain stem lesions in sporadic Creutzfeldt–Jakob disease: A histopathological and immunohistochemical study

Lesions of the brain stem in sporadic CJD were histopathologically and immunohistochemically investigated using an anti‐PrP antibody on ten consecutive autopsy cases. Three major histopathological changes, spongiform changes, neuronal loss and hypertrophic astrocytosis, were employed as parameters of the alterations. The quadrigeminal plate and pontine nuclei were the most severely and consistently affected structures, and immunoreactivity against PrP was seen in these structures. There existed some discrepancies between the severity of the lesions and the intensity of the immunoreactivity against PrP. The medulla oblongata essentially remained normal on histopathological examination, but the inferior olivary nucleus showed prominent PrP deposition. Although the general view that pathological alterations in the brain stem are relatively mild in sporadic CJD was confirmed in this study, lesions of variable degrees which might influence a patient's clinical course were still observed in many structures in the brain stem.     

Gamma-aminobutyric acid-immunoreactivity in the rat hippocampus. A light and electron microscopic study with anti-GABA antibodies

The distribution of GABA-immunoreactive neurons and axonal varicosities was investigated in the hippocampal region of the rat brain by means of an indirect peroxidase immunocytochemical method with recently developed anti-GABA antibodies. The immunolabeling was found to be restricted to nervous structures: neuronal cell bodies, dendrites and axon terminals. Myelinated axons showing GABA-immunoreactivity were also observed. GABA-immunoreactive neurons were found in great number in the stratum pyramidale, the superficial part of the stratum oriens and the deep part of the stratum radiatum in the Ammon's horn. Less were found in the other regions; rare labeled cells were observed in the superficial part of the stratum radiatum and the middle part of the stratum oriens. The dentate gyrus exhibited numerous labeled cells in the granular layer, few in the hilus, rare in the molecular later. A high density of GABA-immunoreactive terminals was found at the limit of the stratum oriens with the alveus, in the stratum pyramidale and in the stratum lacunosum. A lower density of labeled fibers was observed in the other areas. The somata and proximal dendrites of pyramidal and granular cells were encompassed by characteristics pericellular arrangements of GABA-immunoreactive varicosities. Ultrastructural observations revealed a diffuse immunoreaction product spread over the cytoplasm and the nucleus without specific relationship with the organelles, and immunoreactive aggregates in the cytoplasm. Labeled dendrites often showed enlargements displaying the immunoreaction whereas thinner segments were devoid of it. They received numerous asymmetrical synapses from unlabeled axon terminals. GABA-immunoreactive terminals were filled with small clear vesicles with immunopositive membranes and were observed in symmetrical contact with somata and dendrites.