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The a-subunit of the clotting factor XIII (FXIIIa) has previously been shown to be synthesized by cells of monocyte lineage such as macrophages and histiocytes. Thus, besides clot retraction, a possible role of FXIIIa has also been postulated in inflammation. In order to test this hypothesis, FXIIIa-expression in granulomatous lesions due to sarcoidosis and mycobacterial infection was investigated. In the 12 cases (six cases each) examined, FXIIIa-positive macrophages were consistently detected by immunohistochemistry. They were predominantly observed in the periphery of granulomas, whereas the centers were generally devoid of these cells. We did not find any difference in the distribution of FXIIIa-positive cells in both conditions; thus FXIIIa did not improve the differential diagnosis between sarcoidosis and tuberculosis. However, FXIIIa-producing macrophages seemed to contribute to the centripetal fibrosis in granuloma. These results further suggest that the basic pathogenetic mechanisms in granuloma formation are very similar, regardless of their origin from sarcoidosis or tuberculosis.

Three cases of primary rhabdoid tumour of the CNS (RT-CNS) are presented. In case 1 a hemispheric tumour developed in a 10.5 months old girl, who survived for 6 months after incomplete resection, radio- and polychemotherapy. Case 2 was a 4 years and 8 months old boy with a large IIIrd ventricle tumour, who died of leptomeningeal tumour dissemination 7 months after diagnosis despite radiotherapy. In case 3 a pineal mass occurring in a 14 month old female was radioresistant and totally exstirpated. The child died due to tumour recurrence two months later. Autopsy examination revealed widespread leptomeningeal dissemination. All three cases fulfilled light and electron microscopic criteria of RT-CNS including abundant eosinophilic cytoplasm, vesicular nuclei with large nucleoli and conspicuous anti-vimentin positive filaments. Extensive immunohistochemical studies showed expression of epithelial (EMA, KL1), macrophage (alpha-1 antichymotrypsin), neuro-ectodermal (GFAP, NSE, beta-tubulin III) and myogenic markers (desmin, actin). Different stress proteins (alpha-B crystallin, HSP70) were also expressed. Tumour cells showed a proliferation (MIB1) index of 28.4% (case 1) and 33.4% (case 2). From our study it can be concluded that RT-CNS reveals significant immuno-morphological heterogeneity thus supporting the view that it is not a specific pathological entity but merely a phenotypic appearance of different neoplasms, some of which are linked to primitive neuro-ectodermal tumours.

A case of temporal desmoplatic ganglioglioma surgically removed in a 17-year-old patient is reported. Immunohistochemistry showed glial and neuronal differentiation of tumour cells. The frequent occurrence of a desmoplastic component in gangliogliomas is stressed. The present case and other reports from the literature confirm that such desmoplastic neoplasms can not be regarded as exclusively infantile tumours, as recently proposed by the WHO-classification of Brain Tumours.

Despite many sensational and intimidating reports in the mass media, transmissible spongiform encephalopathies (prion diseases) are not contagious in the usual sense. Successful transmission requires both specific material (an affected individual's tissue, from or adjacent to CNS) and specific modes (mainly penetrating contact with the recipient). Nevertheless, specific safety precautions are mandatory to avoid accidental transmission and to decontaminate any infectivity. The autopsy is essential for definite diagnosis of these disorders. Recommendations are given here for safe performance of the autopsy, for neuropathology service and appropriate decontamination; they are based on the current literature and on precautions taken in most laboratories experienced in handling tissue from transmissible spongiform encephalopathies. In essence, special care must be taken to avoid penetrating wounds, possible contamination should be kept to a minimum, and potentially infectious material must be adequately decontaminated by specific means. The full English text of this Consensus Report was published in Brain Pathology 5: 319-322 (1995).

A case of Gerstmann-Sträussler-Scheinker syndrome observed in a 54 year-old woman is reported. The disease lasted over 4 years and was mainly characterized by ataxia and progressive dementia. The patient belongs to a Sicilian family and some of her relatives have been (or still are) affected by similar clinical syndromes. The neuropathological investigation disclosed an impressive number of PAS-positive amyloid deposits (plaques) in the cortex of the cerebrum and in particular of the cerebellum, in the basal ganglia and thalami as well. These plaques were of different size and morphology: multicentric and Kuru-like, cotton-wool and Alzheimer-like, compact and punctate. In some of them, remnants of dystrophic neurites were detected with ubiquitin-reaction and with the metallic method of Gallyas. No reactions were observed with tau-protein, GFAP and Campbell's method. The immunohistochemical investigations for prion-protein, kindly performed by Prof. Kretzschmar (Goettingen) confirmed that the plaques did not contain beta-protein A4, but reacted positively with anti-prion-protein. These results confirmed the diagnosis of GSS syndrome. The importance on an exact neuropathological investigation employing immunohistochemical reactions and metallic methods in every case of progressive degenerative encephalopathy with PAS-positive (amyloid) deposits (dementia of Alzheimer type, suspected Prion-encephalopathies, etc.) is emphasized. Potential infectivity of the tissue in prion-encephalopathies is deactivated soaking the blocks for histology in formic acid (95-100%) for one hour, followed by formalin for at least three days. Moreover the pretreatment with formic acid does enhance the positivity of PAS-reaction.

The results of immunohistochemical detection of p53 protein in a large variety of CNS neoplasms with the polyclonal antiserum CM1 are presented. Immunoreactivity in at least several cells were regularly found in astrocytic neoplasms including glioblastomas; it was also frequent in medulloblastomas and oligodendrogliomas and could be found in more than 50% of acoustic schwannomas and esthesioneuroblastomas. Meningiomas also showed several immunoreactive cells in about 40% of the cases. Certain neuronal/neuronal-glial tumours (such as central neurocytomas, dysembryoplastic neuroepithelial tumours, gangliocytomas, dysplastic gangliocytomas of the cerebellum etc.) were consistently negative, whereas gangliogliomas (with the exception of the regularly positive desmoplastic gangliogliomas) very rarely displayed immunoreactive glial cells. Positive findings, however, seem to be more frequent in anaplastic gangliogliomas where they may be of prognostic significance. The same may be valid in ependymomas. The underlying mechanism for p53 immunopositivity, however, can be very heterogeneous and possibly even contrary (either accumulation of inactive mutant protein or detection of active wild-type protein), therefore isolated immunohistochemical findings call for very cautious interpretation.

Neuropathological diagnostic criteria for Creutzfeldt-Jakob disease (CJD) and other human transmissible spongiform encephalopathies (prion diseases) are proposed for the following disease entities: CJD--sporadic, iatrogenic (recognised risk) or familial (same disease in 1st degree relative): spongiform encephalopathy in cerebral and/or cerebellar cortex and/or subcortical grey matter; or encephalopathy with prion protein (PrP) immunoreactivity (plaque and/or diffuse synaptic and/or patchy/perivacuolar types). Gerstmann-Sträussler-Scheinker disease (GSS) (in family with dominantly inherited progressive ataxia and/or dementia): encephalo(myelo)pathy with multicentric PrP plaques. Familial fatal insomnia (FFI) (in member of a family with PRNP178 mutation): thalamic degeneration, variable spongiform change in cerebrum. Kuru (in the Fore population). Without PrP data, the crucial feature is the spongiform change accompanied by neuronal loss and gliosis. This spongiform change is characterised by diffuse or focally clustered small round or oval vacuoles in the neuropil of the deep cortical layers, cerebellar cortex or subcortical grey matter, which might become confluent. Spongiform change should not be confused with non-specific spongiosis. This includes status spongiosus ("spongiform state"), comprising irregular cavities in gliotic neuropil following extensive neuronal loss (including also lesions of "burnt-out" CJD), "spongy" changes in brain oedema and metabolic encephalopathies, and artefacts such as superficial cortical, perineuronal, or perivascular vacuolation; focal changes indistinguishable from spongiform change may occur in some cases of Alzheimer's and diffuse Lewy body diseases. Very rare cases might not be diagnosed by these criteria. Then confirmation must be sought by additional techniques such as PrP immunoblotting, preparations for electron microscopic examination of scrapie associated fibrils (SAF), molecular biologic studies, or experimental transmission.

A 54-year-old female patient with a 10-year history of ventriculoperitoneal shunt resulting from communicating hydrocephalus of undetermined aetiology is reported. Transient gait disturbances and cerebral infarction at the age of 46 did not lead to further insights into the nature of the disease. After many years with only occasional disturbances, a distinct organic brain syndrome developed. Thorough examination led to a tentative diagnosis of neurocysticercosis; this was based on the history, liquor diagnosis and cerebral microcalcifications in CT. Despite the initiation of specific therapy, the patient died of the sequelae of the disease. At autopsy, characteristic cicatricial residues of mainly basal leptomeningitis were found with collapsed parasitic cysts. Additional intracerebral mesenchymal-glial reactions were less conspicuous. Residual ependymitis had caused aqueductal stenosis. Death was due to cachexia, bronchopneumonia and a lung abscess. The clinical course and morphology of neurocysticercosis are discussed. The disease has become rare in our country, but is globally the most important parasitic disease of the central nervous system.

A 59-year-old male patient was transnasally operated on because of a pituitary adenoma with hypopituitarism. A second operation and X-ray therapy followed a half year later due to recurrent tumor. Both neoplasmas were classified as sparsely granulated prolactin cell adenomas. Immunohistochemical studies revealed strong immunoreactivity for prolactin and FSH in the tumor cells of both the pituitary adenoma and the recurrent tumor. Two years later the prolactin plasma levels were extremely elevated. A tumor in the liver was identified. Biopsy revealed a solid endocrine tumor containing prolactin by immunohistology. Due to structural and immunohistological similarities this tumor could be identified as a metastasis of the pituitary tumor. After 5 months of therapy the patient died from thrombembolism. Post-mortem studies confirmed the diagnosis of a metastasizing prolactin-secreting pituitary carcinoma. Only six similar cases have been reported in the literature. Our case report confirms the experience with 35 definite pituitary carcinomas reparted in the current literature: malignant pituitary tumors develop after pituitary surgery and can be identified not from the pituitary tumor, but only from its metastases.

Despite many sensational and intimidating reports in the mass media, transmissible spongiform encephalopathies (prion disease) are not contagious in the usual sense. Successful transmission requires both specific material (an affected individual's tissue, from or adjacent to CNS) and specific modes (mainly penetrating contact with the recipient). Nevertheless, specific safety precautions are mandatory to avoid accidental transmission and to decontaminate any infectivity. Autopsy is essential for definite diagnosis of these disorders. Recommendations are given here for performance of the autopsy, for neuropathology service and appropriate decontamination; they are based on the current literature and on precautions taken in most laboratories with experience in handling tissue from transmissible spongiform encephalopathies. In particular, special care must be taken to avoid penetrating wounds, possible contamination should be kept to a minimum, and potential infectious material must be adequately decontaminated by specific means.

A 6-year-old girl had progressive ataxia, and visual disturbances resulting in blindness. She died in her sleep at age 22 years. She shared with her sister and paternal relatives bilateral pes cavus deformities and impaired deep-tendon reflexes which suggested Charcot-Marie-Tooth disease. Her sister, who also had both polyneuropathy and a progressive central nervous system (CNS) disease, did not have pigmentary retinopathy. At autopsy, the patient was found to have neuronal ceroid-lipofuscinosis (NCL) marked by intraneuronal accumulation of autofluorescent granular lipopigments in ballooned perikarya and conspicuous extraneuronal pigmentation of subcortical grey matter, but without axonal spheroids. These findings indicate a pigment variant of NCL and represent one of very few patients recorded. The ultrastructure of the intraneuronal pigments was uniformly granular, while that of the extraneuronal pigments found within processes of the neuropil and glial perikarya was more variegated. In addition to those patients with the pigment variant of NCL, described earlier by Jakob and Kolkmann [1973: Acta Neuropathol (Berl) 26:225-236], and Jervis and Pullarkat [1978: Neurology 28:500-503], our patient shared clinical symptoms with those described in a family afflicted with polyneuropathy and NCL by Wisniewski et al. [1987: J Child Neurol 2:33-41]. Currently, it is unclear whether they have similar atypical forms of juvenile NCL (JNCL). We conclude that the spectrum of pigment variants in lysosomal diseases is heterogeneous: only few and recently described patients have had NCL, while others most likely had other forms of lipidosis.

The histological examination of a meningioma-like tumour operatively removed from the left frontoparetial region of a 4-months-old baby, disclosed a high-cellular malignant neoplasia built up by streams of elongated spindle-shaped cells, and with a predominant storiform-pattern as usually seen in malignant fibrous histiocytoma (MFH). Immunohistochemical reactions for alfa-I-ACT and Lys were negative; tumor cells expressed vimentin. Electronmicroscopy disclosed fibroblast-like cells. This tumour was compared with a recurring malignant fibroblastic meningioma characterised, in the recurrence, by storiform areas. In this second tumour, alfa-I-ACT was highly positive. Questions concerning the occurrence of primary cerebral MFHs are discussed. The immunohistochemical findings in-the tumours of the present investigation underline the not-specificity of so-called histiocytic markers.

A case of dysembryoplastic neuroepithelial tumour of the cerebellum occurring in a 28-year-old woman is presented. The lesion extended from the cortex of the inferior vermis upwards into the white matter. Histologically, it exhibited areas of microcystic cerebellar astrocytoma and glial regions with hamartomatous blood vessels as well as areas with oligodendrocyte-like cells (OLC) with a delicate, fibrillary stroma lying in a mucinous, often microcystic matrix. The OLC showed prominent rosette formation and immunohistochemical features suggesting neuronal, i.e. granule cell, differentiation.

This report presents a case of infantile multiple system atrophy with probably autosomal recessive inheritance. The female patient developed generalized muscular hypotonia, myoclonias and tonic-clonic seizures at the age of 8 months, followed by gradual development of choreoathetotic hyperkinesia and increasing psychomotor retardation. Metabolic disease was ruled out and the child died of aspiration pneumonia at the age of 5 years. General autopsy was unremarkable, but neuropathological examination showed degeneration of cerebellum, inferior olives, medial thalamus, Clarke's nucleus, anterior horn cells, corticospinal, spinocerebellar tracts, and posterior columns. Immunohistochemically many neurons contained intranuclear and intracytoplasmic ubiquitin-positive inclusions, which did not contain neurofilament or tau epitopes and ultra-structurally consisted of granulofilamentous material. We tentatively classify this case as a form of infantile multiple system atrophy linked to neuronal intranuclear hyaline inclusion disease.

Two pineal parenchymal tumors are presented, arising in a 54-year-old man and a 72-year-old woman; respectively. They showed isomorphic, cellular areas of small cells, often with characteristic pineocytomatous rosettes, and of medium-sized cells, as well as less cellular regions with highly pleomorphic, often ganglioid large cells. Immunohistochemistry disclosed extensive neuronal differentiation. There was intense positivity for neurofilament protein and microtubule-associated protein 2 in the pleomorphic areas and more variable expression in the isomorphic regions. Diffuse synaptophysin positivity was seen, accentuated along the borders of pleomorphic cells and in the rosettes, as well as diffuse interstitial and/or cytoplasmic expression of neuron-specific enolase, PGP 9.5 and tau. beta-Tubulin III was detected in most cells and slight positivity was found in the rosettes. Expression of glial fibrillary acidic protein, however, was restricted to resident astrocytes and an interstitial network of processes. These neuronally differentiated pleomorphic pineocytomas underline the broad histomorphological spectrum of pineal parenchymal tumors.

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.(ABSTRACT TRUNCATED AT 250 WORDS)

Ocular symptoms are frequently observed in Walker-Warburg (WWS) and associated syndromes. The majority of patients present with malformations of the anterior segment and severe retinal dysplasia. We report on the findings in a female patient with WWS who died at the age of 9 months. Major ocular findings were: severe iridocorneal malformation, a membrane-like structure of the lens and funnel-shaped retinal dysplasia. The retina presented various grades of differentiation with rosettes and atypical sequences of cells, e.g. ganglion cells intermingled between granular layers. The anterior part of the retina presented as a primitive homogeneous layer with a cell-free space that might be interpreted as the primary optic ventricle. This finding suggests that we are dealing with a primary dysplastic non-attachment rather than a real detachment of the retina in WWS. The malformation of the anterior segment was not typical of the Peters' anomaly, as usually described in WWS, but of Rieger's syndrome.

We report on a 39-year-old man with neurofibromatosis-Noonan syndrome and long-standing infertility. Comprehensive testing did not uncover any significant endocrine abnormalities, but the testicular seminiferous epithelium was found to be severely compromised. While the occasional association of neurofibromatosis with signs of Noonan syndrome has been reported, reproductive failure has not been previously described in this condition.

The suitability of Excimer laser beam for microneurosurgery was investigated in an animal experimental study. Cranial bones, cortex and the nervus ischiadicus of the rat were irradiated with 193 nm argon fluoride, 248 nm krypton fluoride, 308 nm xenon chloride and 351 nm xenon fluoride. After survival times of up to 30 days microscopic and electron optic findings of laser lesions at the tissues mentioned above, were studied. By means of the Excimer laser beam high precision tissue effects without or with only low thermal damage to the surrounding tissue were produced with any desired depth of penetration or extension. In analogy with the experiences gathered from animal experiments, a possible use is discussed for the removal of bone tissue around cranial nerves or vascular structures, of epileptogenic foci, or for cutting off pathways in pain surgery (e.g. the zone of entry of the dorsal root of spinal nerves).

Paraneoplastic limbic encephalitis is seldom mentioned in the psychiatric literature and premortem diagnosis is rare. Affective symptoms, agitation, and memory impairment are the core features, which can predate the diagnosis of carcinoma. We report the case of a patient with bronchial carcinoma, whose clinical picture could hardly be distinguished from that of endogenous schizophrenia.

In a neuropathological autopsy study of 21 cases of AIDS-associated PML no fundamental morphological differences to non-AIDS PML were found. PML in AIDS often showed very large foci as well as necrotizing lesions. Partial involvement of cerebral cortex and deep gray matter were common findings; infratentorial lesions could be observed in more than three quarters of cases. Perivascular mononuclear infiltrates within PML foci were frequent and obviously not associated with a more benign clinical course. Possible reasons for these peculiarities of PML in AIDS are discussed. In 7 cases evidence of concomitant HIV encephalopathy was found; this may be one relevant factor contributing to severity of PML in AIDS. PML has to be regarded as a common complication of HIV infection, which may show atypical morphological and neuroradiological features.

Vacuolar myelopathy belongs to the AIDS-associated diseases. It is characterized by vacuolation and infiltration of the long tracts of the spinal cord by macrophages. The clinical and morphological findings of 8 AIDS-patients with vacuolar myelopathy are reported here. The syndrome developed during the final stages of AIDS and was associated with HIV-encephalopathy in 5 cases. The vacuoles were mainly due to intramyelinic swelling and vacuolation. Vacuolated macrophages and axons contributed only to a minor degree. In one case only, HIV-antigens were detected immunohistochemically. The results are discussed in the light of modern pathogenetical concepts of HIV-related diseases.

Two supratentorial desmoplastic gangliogliomas arising in a 15-year-old boy and a 25-year-old man are reported. Both tumors reached the brain surface and exhibited large cysts. They showed intense desmoplasia and tumor cells of astrocytic and ganglionic differentiation. In one case the ganglionic nature was only demonstrable by immunohistochemistry. Such neoplasms can no longer be regarded as exclusively infantile brain tumors.

A case of motor neuron disease (MND) with pallido-luysio-nigral atrophy (PLNA) is reported. The 45-year-old male patient presented with lower motor neuron symptoms and signs of basal ganglia disturbance. He died after a progressive course of 7 months. Neuropathological examination revealed motor neuron loss at all spinal cord levels with sparing of Onuf's nucleus. Nerve cell loss and gliosis were also present in substantia nigra, globus pallidus, and subthalamic nucleus. The presence of ubiquitin-positive inclusions, a hallmark of most variants of MND, confirms this case as an example of MND. At immunoelectron microscopy the granules were distributed on filamentous material. The combination of clinically apparent PLNA with MND has only been described twice previously. The relationship of this syndrome to other forms of MND and its nosological placement are discussed.

Very long chain fatty acids (VLCFA) were found to be markedly increased and phytanic acid was borderline above normal in formalin-fixed brain white matter of case with an unusual type of familial leukodystrophy with epitheloid cells as described previously by Gullotta et al. [Neuropädiatrie (1970) 2: 173-186]. Increased VLCFA in brain clearly demonstrate that the patient had suffered from a peroxisomal disease. This diagnosis is corroborated by ultrastructural findings in brain showing typical lamellar inclusions. The particular type of peroxisomal disorder present in case (heterozygote of X-linked adrenoleukodystrophy?) remains speculative.

Rat monoclonal antibody MS-44B was raised against the dendritic human melanoma cell line SK-Mel 25 and detects highly dendritic cells and endothelial cells in various human organs. Among the cells recognized are dendritic cells in lymphoid organs, such as lymph node, tonsil and spleen, dendritic cells in skin, lung and lamina propria, (astro-)glial cells in the central nervous system and mesangial cells in the kidney. In peripheral lymph nodes (and less consistently in visceral lymph nodes), MS-44B reactive cells are found predominantly in the paracortical area and in the region of the marginal sinus; in tonsils these dendritic cells are concentrated at the outer rim of the follicle, while their distribution in the white pulp of the spleen is less well defined. In skin, both dermal and epidermal dendritic cells are stained. In the dermis just beneath the dermal-epidermal border, dendritic cells may be found with their processes protruding into the epidermal basal layer. MS-44B reactive epidermal dendritic cells send their processes in a horizontal direction or into the upper epidermal cell layers. MS-44B reactive epidermal dendritic cells are neither Langerhans cells, since they lack HLA-DR antigens and CD1, nor Merkel cells, since they lack cytokeratin expression. They rather seem to constitute a subpopulation of epidermal melanocytes that are low in tyrosinase expression and do not populate the melanocyte area of the hair bulb. With regard to the endothelium, monoclonal antibody MS-44B reveals marked heterogeneity in that it preferentially stains the endothelium of large and medium-sized arterial vessels, while capillary and venous endothelia are less well stained.(ABSTRACT TRUNCATED AT 250 WORDS)

A case of progressive multifocal leukoencephalopathy (PML) is reported, detected at autopsy of a 30-year-old patient. The clinical picture was characterized by a progressive course of mental deterioration and ingravescent neurological symptoms. The patient was HIV-negative. He died of bronchopneumonia, after a clinical course of 13 months. Autopsy disclosed pulmonary tuberculosis with involvement of regional lymph nodes. In the brain, besides numerous PML-foci of varying age and structure, a pleomorphic astrocytoma was found in the white matter of the right parietal lobe. In the brain stem glial proliferation resembling diffuse gliomatosis was also present. In situ hybridization revealed Papova-virus (JCV) in oligoglial nuclei, but not in neoplastic astrocytes. This is the third report on the concomitant occurrence of PML and glioma in man.

Neurofibromatosis (NF) is subdivided into at least two different forms: NF-1, which is characterized by café-au-lait spots, cutaneous neurofibromas, Lisch nodules and osseous dysplasias, and NF-2, the hallmarks of which are bilateral acoustic neuromas. Neuropathological findings in 5 cases of NF-1 and 3 cases of NF-2 are presented.

This report describes a sporadic late-onset myopathy in two unrelated adults which was marked by polyglucosan inclusions surrounded by abnormally structured mitochondria, the latter finding a localized, possibly reactive phenomenon. The polyglucosan material was characterized by a battery of histochemical and enzyme histochemical techniques; revealed common antigenicity with Lafora bodies, corpora amylacea and muscle fiber inclusions in types IV and VII glycogenoses; and contained ubiquitin. Additional lectin histochemical and associated digestion preparations disclosed the presence of alpha-glycosyl residues as apparently the sole carbohydrate component in polyglucosan bodies while the above mentioned common antigenicity with Lafora bodies and other inclusions suggests an additional, so far unidentified, protein component.

The autopsy findings in 3 cases of type I ("classical") and 3 of type II ("hydrocephalic") lissencephaly are presented. The characteristic pathomorphology is described and some aspects about pathogenesis are considered.

Several neurodegenerative diseases, including motor neuron disease (MND), are characterized by formation of abnormal cytoskeleton-derived inclusions which contain ubiquitin (Ubq). We have studied the distribution of Ubq in 26 cases of MND with light and electron microscopic immunocytochemistry. Ubiquitin-positive inclusions were found in neurons of anterior horns in most cases of amyotrophic lateral sclerosis (ALS) but were not present in other forms of MND. Ubiquitin immunoreactivity was observed in 10-15 nm intraneuronal filaments, which were not stained by antibodies to neurofilaments, and on dense bodies of dystrophic neurites throughout the neuropil of anterior horns and pyramidal tracts. Data analysis showed a trend toward lower percentage of Ubq-positive neurons in cases with longer duration of illness or lower number of neurons. A high percentage of Ubq-positive inclusions occurred in cases with an aggressive clinical course, suggesting that ubiquitination takes place at early stages of the disease.

The central nervous system of HIV-seropositive patients with and without AIDS-encephalopathy was investigated by immunocytochemistry using the monoclonal antibody to the HIV-1 p24 core protein. Numerous p24-immunopositive mono- and multinucleated macrophages could only be detected in patients with typical histological pictures of an AIDS-encephalopathy. These findings allow the supposition that AIDS-dementia is a result of a relatively late infiltration of HIV-infected macrophages from the bloodstream into the brain and is not due to an impairment of neuronal and/or glial cells infected by HIV during the early stage of the disease.

15 autopsy cases of PML in AIDS are presented. Frequent findings were: Very large, confluent PML-lesions (7 cases), lesions with prominent necrotic features (10 cases) and with marked perivascular mononuclear infiltrates (6 cases). In 9 cases additional PML-foci were seen in the cerebellum and/or the brain stem, and in 1 case there was even an exclusive involvement of those structures. Such characteristics regarding severity and topography of PML in AIDS, may be due to additional toxic factors. In 7 cases HIV-encephalopathy with multinucleated macrophages was present.

Three cases of neuroradiologically diagnosed "leucoencephalopathy" are reported. Histopathological examination disclosed Binswanger's encephalopathy in Case 1, congophilic angiopathy with secondary leucoencephalopathy in Case 2, and HIV encephalopathy with secondary white matter changes in Case 3. These three cases demonstrate the unspecificity of neuroradiological findings in "leucoencephalopathy".

Neuropathological investigations were carried out on 166 autopsies of HIV-seropositive patients, with and without AIDS. Opportunistic infections and lymphomas were present in about 50% of cases; 65 patients were bearers of HIV-encephalopathy. HIV core protein p24 was detected in few mono- and multinucleated macrophages (HIV-cells), only in cases with HIV-encephalopathy. In the CNS of HIV-positive, asymptomatic patients no histological or immunohistochemical abnormalities were seen. These findings let suppose that AIDS-Dementia is a result of a late infiltration of HIV-infected macrophages from the bloodstream into the brain and not due to an impairment of neuronal or glial cells infected by HIV in the early stages of the disease.

After an uneventful pregnancy and labour one hour post partum a tonic-clonic seizure occurred in a female infant. In the following time a muscular hypertonicity developed and the statomotor development ceased. No clue for a neurometabolic disease was found and the child died of an aspiration pneumonia at 5 months of age. Neuropathological examination disclosed a Dentato-Rubro-Pallido-Luysium-Atrophy (DRPLA). Apart from two healthy siblings an older sister had died six months old after an almost identical clinical course. No autopsy was done in this first case. DRPLA is a rare systemic degeneration and begins to our knowledge always in adolescence or adult age. The nosological classification of this unusual case is discussed and the literature is reviewed.

In the past, contradictory results have been reported concerning the specificity of neuronal or glial cell markers. However, we have investigated this aspect in a large group of more than 550 brain tumors (among them 60 medulloblastomas). These contradictions can easily be explained by considering two basic facts. First, every neoplastic cell population, especially in embryonic tumors, diffusely infiltrates the brain tissue: non-neoplastic cells, intermingled with tumor cells, can therefore give rise to immunohistochemical and histogenetic misinterpretations. Second, different cell markers can be expressed by one and the same cell (e.g., GFAP, NSE, vimentin), making nosological interpretation of the tumor difficult, impossible, or at best rather subjective. Clear-cut marker positivity is mostly found in the differentiated tumors for which the nosological classification is already clear by the usual histological methods. Only synaptophysin seems to be a reliable marker for neurogenic cells. In embryonic brain tumors (so-called PNET), no correlations between the presence of a given cell marker and the biological behavior of the tumor have so far been detected.

Samples of the hippocampus of four patients with Down's syndrome [two men aged 35 and 36 years with no evidence of Alzheimer's disease (AD) and two patients aged 47 and 55 years with associated AD] were obtained at post mortem and processed according to the rapid Golgi method. A significant reduction in the number of dendritic spines (DS) was found in the apical (middle, distal and oblique segments) and basilar (thick and thin segments) dendritic arbors of CA1 and CA2-3 pyramidal neurons in patients with Down's syndrome and no AD when compared to age-matched controls. An additional decrease of DS in every segment occurred in Down's patients with associated AD when compared to age-matched controls and Down's patients with no AD. In Down's syndrome (either associated or not to AD) thin basilar dendrites were the most severely involved; in AD patients CA1 pyramids were more severely affected than pyramidal neurons of the CA2-3 subfield.

Lissencephaly is a brain malformation manifested by a smooth cerebral surface and caused by incomplete neuronal migration. Clinical sequellae include minor craniofacial changes (bitemporal hollowing, small jaw), severe mental retardation, and other neurological abnormalities. Patients with classical or type I lissencephaly and its sequellae but no other significant anomalies are classified as having isolated lissencephaly sequence. Possible causes of isolated lissencephaly sequence include ischemia or viral infection during the time of neuronal migration, microdeletion within the Miller-Dieker syndrome critical region in chromosome band 17p13.3, and Mendelian inheritance. The last is based on a report of a single family with three affected children in 1933. We report four patients with isolated lissencephaly sequence from two unrelated families who provide further support for autosomal (or possibly X-linked) recessive inheritance. In the first family, three brothers were affected. In the second, the parents are first cousins.

Extracerebral and cerebral pathology in AIDS (with particular emphasis on the opportunistic infections). The Authors present the extracerebral pathology of 27 cases of AIDS observed at the Department of Pathology of Milan and the cerebral pathology of 80 cases of AIDS collected by three Institutes (Department of Pathology of Milan, Department of Pathology of Rimini and Department of Neuropathology of Münster) with particular emphasis on the pathology of the opportunistic infections. In the adults' group, the most frequent infections are the protozoan ones (T. gondii) followed with equal incidence by the viral and fungal diseases. In the pediatric group the viral diseases are the most frequently seen. Almost all of the adults show multiple infections in the same organ or in different organs. Diffuse lesions with heavy pathologic fields were observed also without tissue reaction. As to cerebral pathology AIDS' patients with opportunistic infections show focal symptoms, whereas the so called "subacute microglial encephalitis" generally appears as a demential syndrome. In cases with progressive multifocal leukoencephalopathy JC virus was always found and in one case also SV 40 - and BK virus. The diffuse demyelinization in some cases of HIV-Encephalopathy is aspecific. In HIV-positive newborns with cerebral signs, the lesions are characterized by oedema, spongiosis and microcalcifications of the basal ganglia; these are aspecific lesions which can be found in toxic and infectious encephalopathies.

10 tumor specimens were processed according to a modification of the AMeX method, which allows for paraffin embedding plus immunostaining of the slices. We used this method to determine the growth fraction of tumors using the monoclonal antibody KI-67. Results were essentially the same as those obtained when studying frozen sections. The quality of the histological slices is equal to frozen sections, but greater areas of tumor can be examined. Furthermore, this method allows for compilation of a stock of tumor specimens which can be used for further immunohistochemical studies whenever needed.

Two cases of striato-nigral degeneration are reported. In case 1 the female patient showed a Parkinson syndrome, cardiac arrhythmias and vasomotor disturbances. Morphologically mainly the putamen and substantia nigra revealed severe atrophic changes according to the restricted form of striato-nigral degeneration (SND). In case 2 there was a disorder of the upper and lower motor neuron in a female patient. Morphologically this case was an example of a multisystem atrophy with changes in the striato-nigral, olivo-ponto-cerebellar systems and spinal motor and autonomic neurons. These cases demonstrate the variability of the striato-nigral degenerations which are met with in two forms: a "pure" form as in case one and as a part of multisystem atrophies. This is underlined in a review of 69 literature cases, which also shows that SND, Shy-Drager syndrome and olivo-ponto-cerebellar atrophy represent very probably different varieties of one and the same degenerative process.

The copper content of astrocytomas and glioblastomas was investigated by the cuproin-method. It could be shown, that the peritumoral tissue of glioblastomas contains more copper than the tumour tissue itself. In astrocytomas, on the other hand, more copper was detected in the central parts of the tumours.

Clinical and ultrastructural findings consisting of curvilinear and fingerprint residual bodies, in a protracted juvenile form of NCL are reported from a woman who died at the age of 35 years. Homochrony and homotypy of her brother's illness emphasize intrafamilial similarities within subgroups of lysosomal disorders.

This report concerns morphologic findings in two middle-aged women, who died of sporadic adult neuronal ceroid-lipofuscinosis (NCL) and whose brains were studied histologically, by electron microscopy and by pigmentoarchitectonic techniques. In addition, the brain of a 35-year-old woman, who died of familial protracted juvenile NCL, was also investigated using pigmentoarchitectonic methods. Clinical, light and electron microscopic findings were compatible with the above-mentioned diagnosis. Pigmentoarchitectural analysis of homotypical isocortex in these three brains revealed (1) loss of pigment-laden stellate cells in layer II, (2) axonal enlargements of layer IIIab-pyramidal cells, and (3) considerable cell loss in layer Va. The changes were more pronounced in the brain affected by protracted juvenile NCL than in the two brains affected by adult NCL. The study emphasizes the value of the pigmentoarchitectonic technique, both in diagnostic neuropathology and in ascertaining patients afflicted with adult NCL. The ultrastructure of the lipopigments showed a motley spectrum of membrane formation such as curvilinear, fingerprint, or straight membranes and was less granular than regular senile lipofuscin.