Showing papers in "Journal of Neuropathology and Experimental Neurology in 1980"

The Axonal Pathology in Chronic IDPN Intoxication

Abstract: Neurofilamentous axonal swellings occur in a number of degenerative and toxic disorders of the nervous system. In one of these, experimental intoxication with beta, beta'-iminodiproprionitrile (IDPN), accumulation of neurofilaments has been shown to result from a defect in slow axonal transport. The consequence of this functional abnormality is a series of changes in axonal morphology: Neurofilaments accumulate in the proximal axon; the proximal axon becomes swollen; the distal axon loses volume (axonal atrophy). These studies indicate that axonal atrophy occurs secondary to an impairment of slow axonal transport and suggest that a similar abnormality may underlie the pathological changes in certain other degenerative and toxic diseases of the nervous system.

Interstitial hyperosmolarity may cause axis cylinder shrinkage in streptozotocin diabetic nerve.

Abstract: Maximal conduction velocity values of nerves of diabetic rats 20 weeks after streptozotocin intoxication were found to be intermediate between those of onset-control and those of end-control groups. The abnormality of conduction velocity of the streptozotocin group might therefore be attributed to a failure of maturation. Detailed electron microscopic morphometry of myelinated fibers (MFs) indicates that more than lack of maturation is involved. Whereas the number of lamellae and the perimeter of axis cylinders of myelinated fibers of the three study groups suggested that growth continues, cross-sectional area of the axis cylinders of the streptozotocin group was smaller than those of either control group. Scored evaluation of fiber shape and the measured index of circularity, which related perimeter and transverse axis cylinder area, also indicated that a selective shrinkage of axis cylinders had occurred. This selective alteration in size and shape of axis cylinders is identical to that described after hyperosmolar fixation. Compared with that of controls, the serum of streptozotocin rats is hyperosmolar. It would seem reasonable to attribute the axis cylinder changes to shrinkage. Whether an additional maturational effect is operative as well cannot be resolved from our data.

Morphology of the developing visual cortex of the human infant: a quantitative and qualitative Golgi study.

Abstract: A renaissance of the Golgi impregnation method has focused interest on dendritic aspects of neuronal development. The visual cortices of 39 "neurologically normal" infants from 14 weeks' gestation to 6 months of age were prepared at postmortem for rapid Golgi impregnation studies. These were stained and duplicated with camera lucida drawings. The total number of cells in defined columns of the visual cortex was counted on cresyl violet-stained sections, and differentiated neurons were identified. The number of spines on the apical and basal dendrites of selected cells was counted for a given interval along the dendrites. The camera lucida drawings, cell counts, and spine counts were used to illustrate the normal ontogeny of the visual cortex.

Local and Distant Neuronal Degeneration Following Intrastriatal Injection of Kainic Acid

Abstract: After intrastriatal injection, the neurotoxin, kainic acid, was cleared from the rat forebrain in a biphasic manner with 70% eliminated within 2 hours; by 24 hours after infusion, less than 1% of the kainic acid remained in the forebrain. The kainic acid diffused into adjacent brain structures, achieving mu molar concentrations in several regions ipsilateral to the injected striatum. At various times after intrastriatal injection of 9.3 nmoles of kainic acid, the brain was serially sectioned; the sections were stained for Nissl substance with cresyl violet or for degenerating neurons with the ammoniacal silver method. Neuronal degeneration spread unevenly into contiguous structures from the central sphere in the injected striatum and affected the ipsilateral pyriform cortex and amygdala, the deep layers of the overlying cerebral cortex, and the medial aspects of the bed nucleus of the stria terminalis and of the nucleus accumbens. In half of the rats, the pyriform cortex contralateral to the side of injection also underwent degeneration. A subpopulation of pyramidal cells in layer IV of the lateral neocortex and the CA3-CA4 pyramidal cells in the ipsilateral hippocampus were selectively affected, whereas adjacent neurons remained intact. The distribution of agyrophilic fibers and terminals in subcortical structures was consistent with the degeneration of neurons of origin in the affected striatal and extrastriatal regions. Brain sections stained by the gold sublimate technique from rats perfused 20 days after injection revealed an intense astrocytic response in all areas affected by acute neuronal degeneration. Extrastriatal damage could be markedly reduced by injection of lower doses of kainic acid (2.3 nmoles) with brief anesthesia; under these conditions, however, the subpopulation of large striatal neurons were relatively resistant, as compared to the Golgi II neurons. These studies demonstrate significant and variable neuronal degeneration beyond the primary site of the lesion after intracerebral injection of kainic acid; several factors affect the pattern of degeneration, including the amount of kainic acid injected, its biological activity, its diffusion, duration of anesthesia, and variable sensitivity of neurons. Consequently, care must be exercised in the use of this neurotoxin to determine the extent and selectivity of neuronal damage, particularly with reference to neuronal vulnerability beyond the central sphere of intrinsic neuronal degeneration.

Pathogenesis of human poliovirus infection in mice. I. Clinical and pathological studies.

Abstract: Human poliovirus infection in mice was studied to determine the similarities to human poliomyelitis, the selective vulnerability of neurons to infection, the role of the immune response in age-dependent susceptibility, and possible viral persistence. Mice inoculated intracerebrally (ic) with the Lansing type 2 poliovirus developed a disease with clinical, pathological, and age-dependent features resembling human poliomyelitis. Adult mice had a shorter incubation period (50% paralysis, Day 8 vs. Day 13) and a higher incidence of paralysis (97% vs. 79%) than newborns. Only paralyzed animals had pathologic changes in the spinal cord, and these corresponded to the degree of paralysis. Fluorescent antibody staining showed that selective infection of neurons was most intense in the anterior horn motor neurons of the spinal cord. There was no extraneural virus replication and no systemic neutralizing antibody response. Cyclophosphamide immunosuppression enhanced rather than diminished disease, indicating that maturation of immune responses did not explain the relative resistance of newborns to paralysis.

The effects of spinal cord trauma on myelin.

Abstract: Experimental spinal cord trauma was produced in rats by dropping a 10-g weight from a height of 30 cm upon exposed spinal cord. The histological lesion consisted of edema, necrosis, and hemorrhage. The fine structure of the early traumatic lesion (4 to 12 hours) included granular dissolution of axons and a characteristic vesiculation of myelin. The predominant ultrastructural features of older lesions (12 to 72 hours) were intra-axonal calcification and lipid-laden macrophages. The yield of myelin and the activity of adenosine 2', 3'-cyclic nucleotide 3'-phosphohydrolase (CNP) were reduced by approximately 15% at 4 hours and by 60% at 72 hours. Losses in all myelin proteins were observed, but were most severe and occurred earliest in the basic proteins. The ultrastructural and biochemical alterations observed in this study indicate that proteinase activity is increased and may be partially responsible for the traumatic myelinolysis in experimental spinal cord trauma.

Axonal Dystrophy in the Gracile Nucleus in Congenital Biliary Atresia and Cystic Fibrosis (Mucoviscidosis): Beneficial Effect of Vitamin E Therapy

Abstract: In 63 patients with malabsorption syndromes, 16 with congenital biliary atresia (BA) and 47 with cystic fibrosis (CF), axonal dystrophy in the gracile nucleus (ADG) was studied. of the 16 patients with BA, ADG of considerable severity was observed in all 10 over one year of age. of the 47 patients with CF, it was observed in 32, 61, and 80% of the cases in the first, second, and third decades, respectively. Evidence is presented that there has been a substantial decrease in the incidence of ADG in CF patients in recent years and that the decreased incidence is attributable to vitamin E (Aquasol E) therapy. The beneficial effect of vitamin E supplementation in CF patients is proffered as strong evidence that ADG in BA and CF is related to vitamin E deficiency. The present study indicates that BA and CF patients require vitamin E supplementation to maintain a normal integrity of axons related to the gracile and perhaps other sensory nuclei. Critical neurological evaluation for possible dysfunction of the sensory nuclei in these patients with malabsorption syndromes is advised.

An unusual degenerative disorder of neurons associated with a novel intranuclear hyaline inclusion (neuronal intranuclear hyaline inclusion disease). A clinicopathological study of a case.

Abstract: A 21-year-old woman with an unusual, progressive, degenerative neurological disorder is described. The disorder is characterized clinically by behavioral abnormality, peculiar involuntary movements, and ataxia starting in early childhood and subsequent development of dementia, choreoathetosis, rectal and bladder incontinence, bulbar and spinal muscular weakness, pes cavus, kyphoscoliosis, and generalized seizures. The clinical manifestations are correlated, with widespread pathological changes affecting almost all neuronal systems. The pathological changes are discussed in relation to the wide spectrum of "multisystem atrophies." Particular attention is directed to the ubiquitous occurrence of a novel intranuclear, eosinophilic, hyaline inclusion in almost all types of central, peripheral, and autonomic neurons. The ubiquitous neuronal involvement seems to explain the diffuse multiple system degeneration. The pathogenesis of the neuronal inclusions is unknown, but it is speculated that the disorder may represent a metabolic abnormality affecting the nuclear protein of neurons, rather than a viral infection. The pathological features, consisting of the neuronal intranuclear hyaline inclusions associated with multiple system atrophy, have not hitherto been described, and "neuronal intranuclear hyaline inclusion disease" is proposed as a name for the disorder. Rectal biopsy demonstrating the intranuclear hyaline inclusions in ganglion cells of the hyenteric plexuses may serve as a diagnostic procedure for the disorder.

Confirmation of virtual unmyelinated fiber absence in hereditary sensory neuropathy type IV.

Abstract: Sural nerves from two unrelated young boys were virtually without unmyelinated fibers (UFs). Small myelinated fibers (MFs) may also have been slightly reduced in number. Since no degeneration or regeneration is observed, UF absence is assumed to be congenital, due to either lack of neuron formation or to premature degeneration. The main clinical features of this inherited sensory neuropathy (previously identified by us as type IV) are the inherited nature and abnormality of nociception, of sweating, and of thermal regulation associated with mild mental retardation. Our findings confirm the congenital absence of UFs of cutaneous nerves in cases such as these and provide further evidence that this disorder has a different natural history and pathology than do the other three types of hereditary sensory neuropathy.

Electron microscopic study of capillary wall in human cerebral edema.

Abstract: Cortical biopsies of 17 patients with diagnoses of congenital malformation, cerebral tumor or brain trauma complicated by subdural hematoma or hygroma were studied with the electron microscope; the alterations of the blood-brain barrier in moderate and severe perifocal cerebral edema were observed. Moderate edema was found associated with central nervous system malformations, while severe edema was seen accompanying brain tumors and serious head injuries. The peripheral cytoplasm of endothelial cells displayed increased formation of microvilli and clear or amorphous electron-dense vacuoles, as well as pinocytotic and coated vesicles. In severe edema, the formation of elongated or chained vacuoles forming transendothelial channels was observed. In moderate edema, endothelial junctions exhibited a tortuous pathway, with a luminal portion sealed by tight junctions and dilated, open, basal portions ending at the basement membrane. In severe edema, the zonulae accludentes partially disappeared and the endothelial junction basal segments became irregularly dilated. The basement membrane showed enlargement, rarefaction, vacuolization, and the presence of collagen fibers. Fine expansion of the basement membrane was distinguished, showing matrix loss and clear, irregularly-dilated channels. Capillaries with reduplicated basement membrane were also observed. The pericytes exhibited edema, vacuolization, and phagocytic activity. In moderate cerebral edema, the clear or dense edematous and vacuolated perivascular end-feet of astrocytes appeared closely applied to the basement membrane, while in severe cerebral edema, they were separated from the basement membrane and showed gradual disappearance of the gap junctions. In all cases, moderately or markedly dilated extracellular spaces were observed in the pericapillary neuropil.

High-Resolution Electron Microscopic Analysis of the Amyloid Fibril in Alzheimer's Disease

Abstract: Examination of brain biopsies from Alzheimer's patients by electron microscopy revealed two types of filaments in and around the argyrophile plaques. The first neurofibrillary tangles were in degenerating neuronal processes, and each twisted tubule was made up of paired helical filaments. The second type stained for amyloid and had the ultrastructural appearance of amyloid. Amyloid fibril material found in these plaques was studied by means of tilt-stage electron microscopy and compared with X-ray images of scale models of bifilar helix. The model fulfilled the structural criteria established by electron microscopy. These observations confirmed that each amyloid profile was composed of a pair of twisted tubules, each of which measured about 60 A in diameter.

Pathogenesis of human poliovirus infection in mice. II. Age-dependency of paralysis.

Abstract: The mechanism of resistance of newborn mice to poliovirus-induced paralysis was studied by comparing regional virus replication in the adult and in the newborn central nervous systems (CNS) after intracerebral (ic) and intraspinal inoculation. Initial virus replication in the brains was similar in both age groups. Paralysis correlated with replication of virus in the spinal cord to a constant threshold, and this replication in newborns was delayed. Intraspinal inoculation of newborns eliminated the delay, indicating that neonatal anterior horn motor neurons were fully susceptible to infection. Cordectomy prevented the spread of virus, despite patent cerebrospinal fluid (CSF) pathways. Thus, poliovirus appeared to spread within the CNS via an axonal transport system. Known maturational changes in the fast transport system may explain the relative resistance of immature mice to poliovirus-induced paralysis.

Effect of Serum Hyperosmolality on Morphometry of Healthy Human Sural Nerve

Abstract: Fascicles of human sural nerve, fixed by immersion in isosmolar 2.5% glutaraldehyde solution and in isosmolar osmium tetroxide and embedded in epoxy, undergo a 10% shrinkage in area when compared with cryostal sections. By contrast, fascicles fixed in hyperosmolar solutions (whether 5.6% glutaraldehyde solution or 2.5% glutaraldehyde raised to the same level of hyperosmolality with sucrose) undergo a 43% shrinkage in area. Axis cylinders of myelinated fibers undergo a selective and severe shrinkage and assume noncircular shapes, the shapes allowing the transverse area to decrease when the perimeter remains unchanged. These studies raise the intriguing question of whether interstitial hyperosmolality in metabolic diseases, such as diabetes mellitus, or in uremia may cause osmotic axonal shrinkage, altered transverse fiber shape, and abnormality of function and structure of nerve.

The endoneurial content of lead related to the onset and severity of segmental demyelination.

Abstract: The endoneurial lead and water content was serially evaluated in the nerves of rats fed lead carbonate and related to the onset and severity of segmental demyelination and remyelination. Lead began to accumulate significantly in the endoneurium by 5 days, reached a maximum level (71 microgram/g dry weight) by 34 days, and then fell to the perineurial level (28 microgram/g dry weight) by 3 months. The water content of endoneurium did not become significantly increased until the 50th day. Extensive teased fiber grading of pathologic abnormalities carried out on the same animals showed that segmental demyelination began between the 20th and 35th days and worsened progressively. This provides the first evidence that high endoneurial lead concentration precedes segmental demyelination and nerve edema. It suggests that the random Schwann cell damage is more likely to be due to a direct toxic effect of lead rather than to a factor associated with edema or increased endoneurial pressure. Contrary to our expectations, lead content does not parallel water content, as would be expected if lead entry into the endoneurium were associated with an abrupt breakdown of the blood-nerve barrier. A further new finding is the decrease in endoneurial lead content at a time when edema and the pathologic lesions are progressing. This may suggest the development of lead removal mechanisms.

Human ontogenesis. I. Ultrastructural characteristics of developing human muscle.

Abstract: Muscle cells of 25 humans fetuses 7, 9, 10, 14, 17, 20, and 24 weeks old were examined by electron microscopy to determine the structural characteristics of developing muscle. Three structurally different levels of maturation of muscle cells, the primitive myotube, the mature myotube, and the immature muscle fibers, have been observed in the process of human ontogenesis. The sequence of morphological changes and the timing of transformation of one form of fetal muscle into a more mature form are presented.

Imaging system for nerve and fiber tract morphometry: components, approaches, performance, and results.

Abstract: This report describes the imaging system that was developed to recognize, count, size, and evaluate shapes of transverse myelinated fiber (MF) profiles in nerves and fiber tracts automatically and by operator interaction. Automatic analysis, without operator interaction, will either miss a variable percentage of small MFs (using thresholds that discriminate against all other tissue profiles) or include most MFs but spuriously detect other tissue profiles (using more sensitive thresholds). Systems such as this must therefore be operator-interactive. The system that was developed will, in a favorable histologic section, automatically detect and border myelin in more than 85% of MFs without inclusion of other tissue elements. The remainder of the MFs are then identified by the operator with the digitizer pen, and the myelin is automatically bordered or, in rare cases, drawn in. Very reliable, reproducible, and rapid measurements of MF number, size, and shape can be obtained with this system. From evaluation of the size and shape of MFs in semithin sections in the light microscope as compared with the same fibers in adjacent thin sections in the electron microscope, measurements by this system can be expressed as if they were obtained on thin sections. Evaluations can be analyzed statistically, with results printed out, displayed on a video screen, and graphed. Such a system will be useful in evaluating and following morphologic changes in number, size, and shape of MFs in development, aging, regeneration, neurotoxicity, and various diseases.

Myelin and glial membrane structures in the optic nerve of normal and jimpy mouse. A freeze-etching study.

Abstract: In order to investigate the myelin and the glial cell membranes in the optic nerve of the mutant mouse “Jimpy,” the method of freeze-etching was applied. The compact myelin lamellae and the first two glial membranes of the mutant, as compared to the normal mouse, show several abnormalities: absence of intramembraneous particles on the P-face, myelin lamellae separated by cytoplasmic layers, vesicular protrusions forming irregular invaginations, and elevations and tight junctions with a discontinuous, zigzag course. Some of these characteristics were found in the membrane of the oligodendroglia cell of the pathological animal, as well. The astrocytic membranes of both normal and Jimpy mice contain two types of gap junctions. The occurrence of one type seems to be increased in the mutant. Freeze-fractured internodal regions of the axolemma are not significantly different from those of normal animals.

Mollaret's recurrent aseptic meningitis: relationship to epidermoid cysts. Light microscopic and ultrastructural cytological studies of the cerebrospinal fluid.

Abstract: Cells, originally called "endothelial" cells, have been described in the cerebrospinal fluid (CSF) of patients developing recurrent aseptic meningitis (Mollaret's meningitis). In an attempt at better establishing their nature, a 6-year-old child was followed for a period of 3 1/2 years. A cytological light microscopic and ultrastructural study was performed on samples of the CSF obtained during 17 attacks. The findings are presented, and the relationship of Mollaret's meningitis to intracranial epidermoid cysts is discussed.

Blood Nerve Barrier in Rat and Cellular Mechanisms of Lead-induced Segmental Demyelination

Abstract: Feeding of lead carbonate to rats causes widespread and reproducible segmental de- and remyelination of myelinated fibers (MFs) of peripheral nerve. Such segmental demyelination might be explained by increased permeability of endoneurial capillaries to serum containing protein-bound lead. The perineurium of control and lead nerves was impermeable to fluorescein-labeled bovine albumin (FBA) and to horseradish peroxidase (HRP). Epineurial capillaries in both conditions allowed HRP to pass freely between and, to a lesser extent, through endothelial cells. Confirming earlier work, endoneurial capillaries of control rats did not appear to allow HRP to pass between endothelial cells, but allowed some to pass by pinocytosis through endothelial cells where it was taken up by macrophages. Contrary to expectation, flooding of the endoneurium with HRP was seen in only 1 of 36 tissue blocks of lead nerves from rats fed 4% lead carbonate for 7 1/2 and 12 weeks. Abundant HRP reaction product was seen in the epineurium in more than half of these tissue blocks. HRP was not generally found in endoneurial fluid, even in lead nerves with marked edema and widespread segmental de- and remyelination. These findings are against a massive breakdown of the blood nerve barrier, so that HRP passes freely into the endoneurium between endoneurial endothelial cells. It was our impression that HRP reaction product was slightly increased in endoneurial endothelial cells and macrophages of lead nerves as compared to control nerves. These studies suggest that there may be an increased transfer of HRP through endoneurial cells in lead neuropathy. The studies do not provide additional evidence that an altered blood nerve barrier is involved in the development of segmental demyelination in lead neuropathy.

Spinal autonomic neurons in Werdnig-Hoffmann disease, mannosidosis, and Hurler's syndrome: distribution of autonomic neurons in the sacral spinal cord.

Abstract: In Werdnig-Hoffmann disease, mannosidosis, and Hurler's syndrome, two groups of neurons (the Onuf's and intermediomedial nuclei) in the ventral horn of the mid-sacral region are found to share common selective sparing or vulnerability with the intermediolateral nuclei of the thoracolumbar and sacral regions of the spinal cord. This finding confirms the previous observations on the characteristic involvement or sparing in Fabry's disease (14), Shy-Drager syndrome (17), amyotrophic lateral sclerosis, anterior poliomyelitis, and neuronal intranuclear hyaline inclusion disease (15), and supports the assumption that the Onuf's and intermediomedial nuclei in the ventral horn represent autonomic neurons much as the thoracolumbar and sacral intermediolateral nuclei.

Human ontogenesis. II. Development of the human neuromuscular junction.

Abstract: The ultrastructural pattern of the early stages of end-plate formation is described in the quadriceps femoris muscle of 9- to 20-week-end human fetuses. Features of the neuromuscular junction are first observed in the ninth week of fetal life. The primitive motor end-plate contains a few axons always covered by one Schwann cell and does not seem to change either in number or in structure from the tenth through the twentieth week. Continuous modification of the post-synaptic apparatus is observed from the tenth to the twentieth weeks of human fetal life.

Primary Intracerebral Tumor with Mixed Chondrosarcoma and Glioblastoma—Gliosarcoma or Sarcoglioma?

Abstract: An unusual primary intracerebral tumor with combined features of chondrosarcoma and glioblastoma multiforme is presented. Glial elements showing a spectrum of hyperplastic and neoplastic changes were intermingled with sarcomatous areas, similar to that recently described by Lalitha and Rubinstein as "sarcoglioma." Many vessels in the gliomatous regions contained proliferating endothelial cells with marked cytologic abnormalities. Although no direct extension out of the vessel wall was conclusively identified, the possibility of sarcomatous change could not be completely excluded. We conclude that, in this case, we could not establish whether the sarcoma was primary and the glioma secondary ("sarcoglioma") or vice versa ("gliosarcoma"), nor could we rule out that the two components originated from the same ancestral pluripotential cells.

Charcot-Marie-Tooth disease associated with hypertrophic neuropathy: a neuropathologic study of two cases.

Abstract: The neuropathologic features of two cases of Charcot-Marie-Tooth disease associated with hypertrophic neuropathy are described. The peripheral nerves had a loss of myelinated fibers, endoneurial fibrosis, and numerous onion-bulb formations. The most severe changes were seen in the distal nerves. In the older of the two patients, advanced changes were also observed in the proximal nerves and anterior roots and were associated with neuronal degeneration in the anterior horns and dorsal root ganglia. The muscles were the site of chronic denervation atrophy, which was most severe in the distal portions of the lower extremities. In one of the cases, the autopsy findings were complemented by sural nerve biopsy studies, which confirmed the presence of segmental demyelination and remyelination, axonal degeneration, and Schwann cell proliferation in the form of onion bulbs. Our observations support the concept of a primary neuronal abnormality in the hypertrophic type of Charcot-Marie-Tooth disease (HN-CMT). The disorder appears to initially involve the distal axonal processes but, with progression of the disease, also involves the proximal axons, eventually leading to degeneration and loss of neurons in the anterior horns and dorsal root ganglia. Onion-bulb formation generally parallels nerve fiber degeneration, suggesting that segmental demyelination and onion bulbs may occur secondary to axonal degeneration. The possibility of a concomitant Schwann cell abnormality cannot be excluded, however, on the basis of our postmortem studies.

The early changes in experimental myopathy induced by chloroquine and chlorphentermine.

Abstract: In soleus muscles of rats treated for 2 to 11 days with high doses of chloroquine or chlorphentermine, muscle fibres showed autophagocytosis followed by segmental contracture and necrosis. Vascuolar degeneration, "splitting", and internal nuclei were absent. At variance with findings in progressive muscular dystrophy, the incidence of intramembrane particles was unchanged and membrane defects in necrotizing fibres were absent. Autophagic vacuoles were formed by cup-shaped cisternae derived from tubules that often enclosed single mitochondria. Golgi complexes occurred in the centre of the fibres; dilated vesicles of the sarcoplasmic reticulum contained an electrondense substance, possibly lysosomal enzymes. Exocytosis of autophagic vacuoles and of almost undigested mitochondria was observed. The changes in the plasma membrane were as in other cells: a bulge was formed that was cleared of intramembrane particles; the membrane fused with the limiting membrane of the autophagic vacuole, the content of which was expelled through an orifice. Inside autophagic vacuoles, persisting phospholipids arranged themselves into protein-free lipid bilayers, that formed concentric membranes or single-layered vesicles. Both drugs are known to inhibit degradation of phospholipids; the findings indicate that the rate of autophagocytosis and exocytosis were enhanced as well. Fibre necrosis was probably due to the fact that fibres eventually became unable to maintain their integrity.

Spontaneous pallido-nigral accumulation of iron pigment and spheroid-like structures in macaque monkeys.

Abstract: Common incidental pathologic findings in Old World monkeys are spheroid-like structures and iron pigment in the substantia nigra and globus pallidus. The occurrence of each finding correlates with the number of years monkeys have spent in captivity. The spheroids are eosinophilic and argyrophilic, but are generally PAS, iron, and luxol fast blue negative. Ultrastructurally, they consist of aggregations of dense globules and granules interspersed with membranes; normal organelles are absent. One classic spheroid with a thin myelin sheath and accumulated fibrillar material was observed. The material in spheroids is ultrastructurally distinguishable from iron pigment, which is present in glial cells, and from neuronal lipofuscin. Accumulation of spheroids and iron pigmentation may be age-related phenomena involving portions of the brain with shared anatomical and biochemical characteristics. The study of these changes may shed light on the pathogenesis of such spheroid degenerations as Hallervorden-Spatz disease.

The Influence of the Ground Substance on the Extracellular Water of Normal and Edematous Human Brain: Focal Edema and the Demyelinating Diseases, Including Multiple Sclerosis

Abstract: The presence of a ground substance in brain provides a mechanism by which edema localized to one region of the white matter might occur without spreading diffusely into the adjacent tissues. The most common such localization is the sparing of the arcuate white matter when the deeper white matter is markedly edematous. This may be related to the higher concentration of mucopolysaccharides in the former. Petechial hemorrhages in the white matter may be surrounded by a zone free of edema, although the hemorrhagic zone itself is almost certainly edematous. This, and the presence of a central zone within some of the petechiae forming a ring hemorrhage may reflect the influence of the ground substance. Focal lesions of the dorsum of the corpus callosum and similar lesions of the basal surface of the pons, these probably due to traumatization by the contiguous falx or arteries, are characterized by myelin loss and axon preservation, a characteristic of edema; the surrounding tissues are not edematous. Severe hypertension is sometimes associated with the presence of clusters of focal perivenous demyelinating lesions in the white matter, the axons being preserved. These resemble the lesions of acute disseminated encephalomyelitis and may be due to edema; they are surrounded by nonedematous white matter. It is suggested that the same concept may apply to the focal demyelinating lesions of acute disseminated encephalomyelitis, multifocal leukoencephalopathy, central pontine myelinolysis and of multiple sclerosis, i.e. the "true" demyelinating diseases, just as has already been suggested for diffuse sclerosis.

Successful silver impregnation of degenerating axons after long survivals in the human brain.

Abstract: Degenerating axons in the human brain were successfully impregnated with reduced silver methods. The appearance of degenerating fibers did not differ markedly with survival times of three weeks and two, six, and twelve years following cerebral infarction or contusion of the brain. Impregnated fibers were found only along the appropriate corticofugal pathways. Electron microscopic examination of Vibratome-cut, silver-stained sections demonstrated silver deposition almost exclusively within axon fragments. Previous studies using anterograde degeneration methods in the human brain have limited their choice of cases to those with short periods of survival. Relaxing the restriction of short survival times extends the range of cases which can be used to study neural connections which may be unique to, or different in, the human brain.

Intracellular inclusions in meningothelial meningioma. A histochemical and ultrastructural study.

Abstract: This is a study on the histochemical and electron microscopic findings of the intracellular inclusions in a case of meningothelial meningioma of the frontoethmoidal region with orbital involvement. The inclusions are PAS-positive, diastase resistant, and stain strongly positive with the modified Morel-Sisley reaction for protein-bound tyrosine and weakly with dihydroxy-dinaphthyl-disulfide (DDD) for the demonstration of sulfhydryl (SH) and disulfide (S-S) groups of proteins. These staining reactions suggest the inclusions are composed of conjugated proteins (glycoproteins). Ultrastructurally, the inclusions are located within intracellular spaces lined by microvilli and are composed of granular material, usually forming a dense core that is intermixed with small vacuoles. Numerous desmosomes and whorls of tonofibrils are concentrated around them. Our findings support the view that the intracellular inclusions, which are rarely found in meningiomas, represent an active secretory product of the meningothelial cells rather than a degenerative or phagocytic process.